PROTEINS

WHAT YOULL LEARN ON THIS PAGE

The importance of proteins
Different functions of proteins within the body
The significance of amino acids as the building blocks of proteins
What a polypeptide chain is and how it is formed
The four levels of structure to proteins
The different types of proteins and how they differ

Proteins are the building blocks of life. They are vital to our existence and are found in every organism on Earth.
Proteins are the most common molecules found in cells. In fact, they constitute more of a cells dry matter
than lipids, carbohydratesand all other molecules combined.
A protein is made from one or more polypeptide chains and each polypeptide chain is built from smaller molecules called
amino acids. There is a total of 20 amino acids that can be arranged in trillions upon trillions of different ways to create
proteins that serve a huge variety of functions.
Proteins are in fact the most structurally complex molecules known to biology.
FUNCTIONS OF PROTEINS
Proteins come in a huge variety of forms and perform a wide range of functions. Examples of proteins include enzymes,
antibodies and some hormones which help to speed up chemical reactions, defend against diseases and regulate the activity
of cells.
Proteins also play a role in movement, structural support, storage, communication between cells, digestion and the transport
of substances around the body.
MOVEMENT
Motor proteins, such as myosin and dyneins, have the ability to convert chemical energy into movement. Myosin is the protein
found in muscle and causes the contraction of muscle fibers in muscles.
Dyneins provide the power that drives flagella. Flagella are long, thin structures attached to the outside of certain cells, such as
sperm cells, and are responsible for their mobility.
STRUCTURE AND SUPPORT
Many proteins provide structural support to specific parts of an organism. Keratin, for example, is the protein found in the
outer layers of skin and makes skin a strong protective layer to the outside world. Keratin is also the structural protein that
makes hair, horns and nails.
CELLULAR COMMUNICATION
Cells communicate with their surrounding environment and other cells. Receptor proteins in a cells membrane receive signals
from outside of the cell and relay messages into the cell. Once the signal is inside the cell it is usually passed between a number
of proteins before it reaches its final destination (also most commonly a protein).
DIGESTION
Digestion is driven by, you guessed it, proteins. Enzymes are proteins that drive digestion by speeding up chemical reactions.
Digestion is the breakdown of food from large, insoluble molecules into smaller molecules that can dissolve into water. As the
smaller molecules are water-soluble they can enter blood and be transported around the body.
Digestive enzymes are the enzymes responsible for breaking down food molecules into smaller, water soluble molecules. Some
examples of digestive proteins include:
Amylase the enzyme in saliva that breaks down starch into soluble sugars
Lipase breaks down fats and other lipids
Pepsin breaks down proteins in food
TRANSPORT OF OXYGEN
Hemoglobin is yet another hugely important protein for animals such as mammals and birds. It is the protein in blood that
binds to oxygen so that oxygen can be transported around the body.
Hemoglobin contains an iron atom. The chemical structure of hemoglobin around the iron atom allows oxygen to bind to the
iron and then be released to oxygen deprived tissue.
As you can see proteins are clearly extremely important to the healthy functioning of an organism. The majority of the
examples I have used are animal proteins but proteins are no less important for other life forms such as
plants, fungi and bacteria.
BUILDING BLOCKS OF PROTEINS
Amino acids are the building blocks of proteins. In total, there are 20 different amino acids found in nature. Amino acids can
link together in a huge variety of ways to create different proteins.
The chemical structure of amino acids is the key to why proteins have become the foundation of life. An amino acid consists of
a carboxyl group (chemical structure -COOH), an amine group (-NH), and a sidechain made mostly from carbon and hydrogen.
The sidechain is often referred to as the R group. Differences in the R group is what makes the 20 amino acids different from
each other.
Depending on the structure of the R group, an amino acid can be water-soluble (polar), water insoluble (non-polar) or contain a
positive or negative charge. These characteristics in turn affect how the amino acids behave as they link up and influences the
overall shape and function of a protein.
All 20 amino acids are necessary for good health. If an organism is low in one of the 20 amino acids, certain proteins will not be
able to be built and the loss of their functions will cause health issues for the organism.
Some amino acids can be created by the body using other molecules while other amino acids must be sourced from food. The
amino acids that must be eaten are known as the essential amino acids because they are an essential part of a healthy diet.
The amino acids that can be made by our bodies are known as non-essential amino acids.
POLYPEPTIDES
A polypeptide is a chain of amino acids and is the simplest form of a protein. Amino acids bond together to form long, linear
chains that can be more than 2000 amino acids long.
The order that amino acids are linked together determines the final shape and structure of the polypeptide chain. A protein will
contain one polypeptide or multiple polypeptides bonded together to form large, complex proteins.
Amino acids are bonded together between the amine group (-NH) of one amino acid and the carboxyl group (-COOH) of a
second amino acid.
As two amino acids bond together, two hydrogen ions are removed from the amine group and an oxygen is removed from the
carboxyl group. The amine group and carboxyl group bond together and a water molecule is produced as a byproduct. The
bond is known as a peptide bond.
Bonding multiple amino acids together by peptide bonds creates a polypeptide backbone with an R group extending out from
each amino acid. As mentioned earlier the R groups of the 20 amino acids each have their own unique structure and chemical
properties. The structure and chemical properties (such as reactivity and boiling temperature) of a polypeptide and ultimately a
protein are determined by the unique sequence of R groups that extend from the polypeptide backbone. As R groups are
attracted or repelled from each other, the polypeptide chain bends and twists into a uniquely shaped protein.
PROTEIN STRUCTURE
Proteins have four levels of structure, all of which we have already alluded to on this page. The four levels are known as the
primary, secondary, tertiary and quaternary structure of a protein.
PRIMARY STRUCTURE
The primary structure is the specific sequence of amino acids i.e. the order that they are bonded together. The exact order that
amino acids are bonded together is determined by the information stored in genes.
Through processes called transcription and translation, DNA provides all the necessary information for cells to produce the
exact primary structure for thousands of different proteins. The primary structure determines the secondary and tertiary
structures of proteins.
SECONDARY STRUCTURE
The secondary structure of a protein is formed by hydrogen bonds between atoms along the backbone of the polypeptide
chain.
Remembering each amino acid has a carboxyl group and an amine group, the slight negative charge on the oxygen of the
carboxyl group forms a weak bond with the slight positive charge of a hydrogen atom on the amine group of another amino
acid. Hydrogen bonds are weak but many of them create enough strength to influence the shape of a polypeptide chain.
The hydrogen bonds cause the polypeptide backbone to fold and coil into two possible forms the helix and the pleated
sheets. An (greek letter alpha) helix is a spiral, similar to the double helix of the iconic DNA strand but with only one coil,
and is formed by hydrogen bonds between every fourth amino acid. The helix is common in structural proteins such as
keratin.
The (greek letter beta) pleated sheets are formed when hydrogen bonds occur between two or more adjacent polypeptide
chains and are common in globular proteins (see below in Types of proteins).
TERTIARY STRUCTURE
The tertiary structure is the final shape that the polypeptide chain takes and is determined by the R groups. The attraction and
repulsion between different R groups bends and folds the polypeptide to create the final 3D shape of a protein.
QUATERNARY STRUCTURE
Not all proteins have a quaternary structure. A quaternary structure only results when multiple polypeptide chains combine
together to form a large complex protein. In such cases, each polypeptide is referred to as a subunit.
Hemoglobin is an example of a protein with quaternary structure. In most animals, hemoglobin is made from four globular
subunits.
TYPES OF PROTEINS
There are four main types of proteins. The most commonly known are the globular proteins. The other three types of proteins
are fibrous, membrane and disordered proteins.
GLOBULAR PROTEINS
A globular protein is any protein that takes a spherical shape in its tertiary structure. These include many enzymes, antibodies
and proteins such as hemoglobin.
Globular proteins are water-soluble and are created due to the attraction and repulsion of different R groups with water. Polar
R groups of the amino acids in proteins are water-soluble while non-polar R groups are water insoluble. Globular proteins form
because non-polar R groups hide in the internal sections of the protein and polar R groups that arrange themselves on the
outer surface that is exposed to any surrounding water.
FIBROUS PROTEINS
Fibrous proteins are elongated proteins that lack any tertiary structure. Instead of bending and folding to form a globular
protein, fibrous proteins remain in their linear secondary structure. They are often important structural and support proteins.
Fibrous proteins are insoluble in water and often have repeating patterns of amino acids along their polypeptide chain.
Examples of fibrous proteins include collagen, keratin and silk.
MEMBRANE PROTEINS
A membrane protein is any protein found within or attached to a cell membrane. They are unique proteins due to the unique
environment that they exist in.
Cell membranes are made from a double layer of phospholipids. The inner parts of a cell membrane is non-polar but the
exterior is polar. In order for membrane proteins to successfully exist across a cell membrane they must contain specific non-
polar and polar sections.
DISORDERED PROTEINS
The discovery of disordered proteins in the early 2000s challenged historical thinking of proteins. Until then it had been
believed that the function of a protein was dependent on its fixed 3D structure. Disordered proteins however exhibit no
ordered structure to their shape.
Some proteins can be fully unstructured whilst other are partially structured with certain unstructured sections. Other proteins
have the ability to exist as disordered proteins only to form a fixed structure after bonding to other molecules.
Proteins
Types and Functions of Proteins
Proteins perform many essential physiological functions, including catalyzing biochemical
reactions.

LEARNING OBJECTIVES

Differentiate among the types and functions of proteins

KEY TAKEAWAYS

Key Points

Proteins are essential for the main physiological processes of life and perform
functions in every system of the human body.
A proteins shape determines its function.
Proteins are composed of amino acid subunits that form polypeptide chains.
Enzymes catalyze biochemical reactions by speeding up chemical reactions, and
can either break down their substrate or build larger molecules from their
substrate.
The shape of an enzymes active site matches the shape of the substrate.
Hormones are a type of protein used for cell signaling and communication.
Key Terms

amino acid: Any of 20 naturally occurring -amino acids (having the amino, and
carboxylic acid groups on the same carbon atom), and a variety of side chains,
that combine, via peptide bonds, to form proteins.
polypeptide: Any polymer of (same or different) amino acids joined via peptide
bonds.
catalyze: To accelerate a process.
Types and Functions of Proteins

Proteins perform essential functions throughout the systems of the human body. These
long chains of amino acids are critically important for:

catalyzing chemical reactions

synthesizing and repairing DNA
transporting materials across the cell
receiving and sending chemical signals
responding to stimuli
providing structural support

Proteins (a polymer) are macromolecules composed of amino acid subunits (the

monomers ). These amino acids are covalently attached to one another to form long
linear chains called polypeptides, which then fold into a specific three-dimensional shape.
Sometimes these folded polypeptide chains are functional by themselves. Other times
they combine with additional polypeptide chains to form the final protein structure.
Sometimes non-polypeptide groups are also required in the final protein. For instance, the
blood protein hemogobin is made up of four polypeptide chains, each of which also
contains a heme molecule, which is ring structure with an iron atom in its center.

Proteins have different shapes and molecular weights, depending on the amino acid
sequence. For example, hemoglobin is a globular protein, which means it folds into a
compact globe-like structure, but collagen, found in our skin, is a fibrous protein, which
means it folds into a long extended fiber-like chain. You probably look similar to your
family members because you share similar proteins, but you look different from strangers
because the proteins in your eyes, hair, and the rest of your body are different.

Human Hemoglobin: Structure of human hemoglobin. The proteins and subunits are in red and blue, and the
iron-containing heme groups in green. From the protein data base.

Because form determines function, any slight change to a proteins shape may cause the
protein to become dysfunctional. Small changes in the amino acid sequence of a protein
can cause devastating genetic diseases such as Huntingtons disease or sickle cell
anemia.

Enzymes

Enzymes are proteins that catalyze biochemical reactions, which otherwise would not take
place. These enzymes are essential for chemical processes like digestion and cellular
metabolism. Without enzymes, most physiological processes would proceed so slowly (or
not at all) that life could not exist.
Because form determines function, each enzyme is specific to its substrates. The
substrates are the reactants that undergo the chemical reaction catalyzed by the enzyme.
The location where substrates bind to or interact with the enzyme is known as the active
site, because that is the site where the chemistry occurs. When the substrate binds to its
active site at the enzyme, the enzyme may help in its breakdown, rearrangement, or
synthesis. By placing the substrate into a specific shape and microenvironment in the
active site, the enzyme encourages the chemical reaction to occur. There are two basic
classes of enzymes:

Enzyme reaction: A catabolic enzyme reaction showing the substrate matching the exact shape of the active site.
Catabolic enzymes: enzymes that break down their substrate
Anabolic enzymes: enzymes that build more complex molecules from their
substrates

Enzymes are essential for digestion: the process of breaking larger food molecules down
into subunits small enough to diffuse through a cell membrane and to be used by the cell.
These enzymes include amylase, which catalyzes the digestion carbohydrates in the
mouth and small intestine; pepsin, which catalyzes the digestion of proteins in the
stomach; lipase, which catalyzes reactions need to emulsify fats in the small intestine;
and trypsin, which catalyzes the further digestion of proteins in the small intestine.

Enzymes are also essential for biosynthesis: the process of making new, complex
molecules from the smaller subunits that are provided to or generated by the cell. These
biosynthetic enzymes include DNA Polymerase, which catalyzes the synthesis of new
strands of the genetic material before cell division; fatty acid synthetase, which the
synthesis of new fatty acids for fat or membrane lipid formation; and components of the
ribosome, which catalyzes the formation of new polypeptides from amino acid monomers.

Hormones

Some proteins function as chemical-signaling molecules called hormones. These proteins

are secreted by endocrine cells that act to control or regulate specific physiological
processes, which include growth, development, metabolism, and reproduction. For
example, insulin is a protein hormone that helps to regulate blood glucose levels. Other
proteins act as receptors to detect the concentrations of chemicals and send signals to
respond. Some types of hormones, such as estrogen and testosterone, are lipid steroids,
not proteins.

Other Protein Functions

Proteins perform essential functions throughout the systems of the human body. In the
respiratory system, hemoglobin (composed of four protein subunits) transports oxygen for
use in cellular metabolism. Additional proteins in the blood plasma and lymph carry
nutrients and metabolic waste products throughout the body. The proteins actin and
tubulin form cellular structures, while keratin forms the structural support for the dead
cells that become fingernails and hair. Antibodies, also called immunoglobins, help
recognize and destroy foreign pathogens in the immune system. Actin and myosin allow
muscles to contract, while albumin nourishes the early development of an embryo or a
seedling.

Tubulin: The structural protein tubulin stained red in mouse cells.

Amino Acids
An amino acid contains an amino group, a carboxyl group, and an R group, and it
combines with other amino acids to form polypeptide chains.

LEARNING OBJECTIVES

Describe the structure of an amino acid and the features that confer its specific properties

KEY TAKEAWAYS

Key Points

Each amino acid contains a central C atom, an amino group (NH2), a carboxyl group
(COOH), and a specific R group.
The R group determines the characteristics (size, polarity, and pH) for each type of
amino acid.
Peptide bonds form between the carboxyl group of one amino acid and the amino
group of another through dehydration synthesis.
A chain of amino acids is a polypeptide.
Key Terms

amino acid: Any of 20 naturally occurring -amino acids (having the amino, and
carboxylic acid groups on the same carbon atom), and a variety of side chains,
that combine, via peptide bonds, to form proteins.
R group: The R group is a side chain specific to each amino acid that confers
particular chemical properties to that amino acid.
polypeptide: Any polymer of (same or different) amino acids joined via peptide
bonds.

Structure of an Amino Acid

Amino acids are the monomers that make up proteins. Each amino acid has the same
fundamental structure, which consists of a central carbon atom, also known as the alpha
() carbon, bonded to an amino group (NH ), a carboxyl group (COOH), and to a hydrogen
2

atom. In the aqueous environment of the cell, the both the amino group and the carboxyl
group are ionized under physiological conditions, and so have the structures -NH and 3
+

-COO , respectively. Every amino acid also has another atom or group of atoms bonded to

the central atom known as the R group. This R group, or side chain, gives each amino acid
proteins specific characteristics, including size, polarity, and pH.
Amino acid structure: Amino acids have a central asymmetric carbon to which an amino group, a carboxyl group, a
hydrogen atom, and a side chain (R group) are attached. This amino acid is unionized, but if it were placed in water at
pH 7, its amino group would pick up another hydrogen and a positive charge, and the hydroxyl in its carboxyl group
would lose and a hydrogen and gain a negative charge.

Types of Amino Acids

The name amino acid is derived from the amino group and carboxyl-acid-group in their
basic structure. There are 21 amino acids present in proteins, each with a specific R group
or side chain. Ten of these are considered essential amino acids in humans because the
human body cannot produce them and they must be obtained from the diet. All organisms
have different essential amino acids based on their physiology.

Types of amino acids: There are 21 common amino acids commonly found in proteins, each with a different R group
(variant group) that determines its chemical nature. The 21st amino acid, not shown here, is selenocysteine, with an R
group of -CH2-SeH.

Characteristics of Amino Acids

Which categories of amino acid would you expect to find on the surface of a soluble
protein, and which would you expect to find in the interior? What distribution of amino
acids would you expect to find in a protein embedded in a lipid bilayer?

The chemical composition of the side chain determines the characteristics of the amino
acid. Amino acids such as valine, methionine, and alanine are nonpolar (hydrophobic),
while amino acids such as serine, threonine, and cysteine are polar (hydrophilic). The side
chains of lysine and arginine are positively charged so these amino acids are also known
as basic (high pH) amino acids. Proline is an exception to the standard structure of an
amino acid because its R group is linked to the amino group, forming a ring-like structure.

Amino acids are represented by a single upper case letter or a three-letter abbreviation.
For example, valine is known by the letter V or the three-letter symbol val.

Peptide Bonds

The sequence and the number of amino acids ultimately determine the proteins shape,
size, and function. Each amino acid is attached to another amino acid by a covalent bond,
known as a peptide bond. When two amino acids are covalently attached by a peptide
bond, the carboxyl group of one amino acid and the amino group of the incoming amino
acid combine and release a molecule of water. Any reaction that combines two monomers
in a reaction that generates H O as one of the products is known as a dehydration
2

reaction, so peptide bond formation is an example of a dehydration reaction.

Peptide bond formation: Peptide bond formation is a dehydration synthesis reaction. The carboxyl group of one
amino acid is linked to the amino group of the incoming amino acid. In the process, a molecule of water is released.

Polypeptide Chains

The resulting chain of amino acids is called a polypeptide chain. Each polypeptide has a
free amino group at one end. This end is called the N terminal, or the amino terminal, and
the other end has a free carboxyl group, also known as the C or carboxyl terminal. When
reading or reporting the amino acid sequence of a protein or polypeptide, the convention
is to use the N-to-C direction. That is, the first amino acid in the sequence is assumed to
the be one at the N terminal and the last amino acid is assumed to be the one at the C
terminal.

Although the terms polypeptide and protein are sometimes used interchangeably, a
polypeptide is technically any polymer of amino acids, whereas the term protein is used
for a polypeptide or polypeptides that have folded properly, combined with any additional
components needed for proper functioning, and is now functional.

Protein Structure
Each successive level of protein folding ultimately contributes to its shape and therefore
its function.
 LEARNING OBJECTIVES

Summarize the four levels of protein structure

KEY TAKEAWAYS

Key Points

Protein structure depends on its amino acid sequence and local, low-energy
chemical bonds between atoms in both the polypeptide backbone and in amino
acid side chains.
Protein structure plays a key role in its function; if a protein loses its shape at any
structural level, it may no longer be functional.
Primary structure is the amino acid sequence.
Secondary structure is local interactions between stretches of a polypeptide chain
and includes -helix and -pleated sheet structures.
Tertiary structure is the overall the three-dimension folding driven largely by
interactions between R groups.
Quarternary structures is the orientation and arrangement of subunits in a multi-
subunit protein.
Key Terms

antiparallel: The nature of the opposite orientations of the two strands of DNA or
two beta strands that comprise a proteins secondary structure
disulfide bond: A bond, consisting of a covalent bond between two sulfur atoms,
formed by the reaction of two thiol groups, especially between the thiol groups of
two proteins
-pleated sheet: secondary structure of proteins where N-H groups in the
backbone of one fully-extended strand establish hydrogen bonds with C=O groups
in the backbone of an adjacent fully-extended strand
-helix: secondary structure of proteins where every backbone N-H creates a
hydrogen bond with the C=O group of the amino acid four residues earlier in the
same helix.

The shape of a protein is critical to its function because it determines whether the protein
can interact with other molecules. Protein structures are very complex, and researchers
have only very recently been able to easily and quickly determine the structure of
complete proteins down to the atomic level. (The techniques used date back to the
1950s, but until recently they were very slow and laborious to use, so complete protein
structures were very slow to be solved.) Early structural biochemists conceptually divided
protein structures into four levels to make it easier to get a handle on the complexity of
the overall structures. To determine how the protein gets its final shape or conformation,
we need to understand these four levels of protein structure: primary, secondary, tertiary,
and quaternary.

Primary Structure

A proteins primary structure is the unique sequence of amino acids in each polypeptide
chain that makes up the protein. Really, this is just a list of which amino acids appear in
which order in a polypeptide chain, not really a structure. But, because the final protein
structure ultimately depends on this sequence, this was called the primary structure of
the polypeptide chain. For example, the pancreatic hormone insulin has two polypeptide
chains, A and B.

Primary structure: The A chain of insulin is 21 amino acids long and the B chain is 30 amino acids long, and each
sequence is unique to the insulin protein.

The gene, or sequence of DNA, ultimately determines the unique sequence of amino acids
in each peptide chain. A change in nucleotide sequence of the genes coding region may
lead to a different amino acid being added to the growing polypeptide chain, causing a
change in protein structure and therefore function.

The oxygen-transport protein hemoglobin consists of four polypeptide chains, two

identical chains and two identical chains. In sickle cell anemia, a single amino
substitution in the hemoglobin chain causes a change the structure of the entire
protein. When the amino acid glutamic acid is replaced by valine in the chain, the
polypeptide folds into an slightly-different shape that creates a dysfunctional hemoglobin
protein. So, just one amino acid substitution can cause dramatic changes. These
dysfunctional hemoglobin proteins, under low-oxygen conditions, start associating with
one another, forming long fibers made from millions of aggregated hemoglobins that
distort the red blood cells into crescent or sickle shapes, which clog arteries. People
affected by the disease often experience breathlessness, dizziness, headaches, and
abdominal pain.

Sickle cell disease: Sickle cells are crescent shaped, while normal cells are disc-shaped.

Secondary Structure

A proteins secondary structure is whatever regular structures arise from interactions

between neighboring or near-by amino acids as the polypeptide starts to fold into its
functional three-dimensional form. Secondary structures arise as H bonds form between
local groups of amino acids in a region of the polypeptide chain. Rarely does a single
secondary structure extend throughout the polypeptide chain. It is usually just in a
section of the chain. The most common forms of secondary structure are the -helix and
-pleated sheet structures and they play an important structural role in most globular and
fibrous proteins.
 Secondary structure: The -helix and -pleated sheet form because of hydrogen bonding between carbonyl and
amino groups in the peptide backbone. Certain amino acids have a propensity to form an -helix, while others have a
propensity to form a -pleated sheet.

In the -helix chain, the hydrogen bond forms between the oxygen atom in the
polypeptide backbone carbonyl group in one amino acid and the hydrogen atom in the
polypeptide backbone amino group of another amino acid that is four amino acids farther
along the chain. This holds the stretch of amino acids in a right-handed coil. Every helical
turn in an alpha helix has 3.6 amino acid residues. The R groups (the side chains) of the
polypeptide protrude out from the -helix chain and are not involved in the H bonds that
maintain the -helix structure.

In -pleated sheets, stretches of amino acids are held in an almost fully-extended

conformation that pleats or zig-zags due to the non-linear nature of single C-C and C-N
covalent bonds. -pleated sheets never occur alone. They have to held in place by other
-pleated sheets. The stretches of amino acids in -pleated sheets are held in their
pleated sheet structure because hydrogen bonds form between the oxygen atom in a
polypeptide backbone carbonyl group of one -pleated sheet and the hydrogen atom in a
polypeptide backbone amino group of another -pleated sheet. The -pleated sheets
which hold each other together align parallel or antiparallel to each other. The R groups of
the amino acids in a -pleated sheet point out perpendicular to the hydrogen bonds
holding the -pleated sheets together, and are not involved in maintaining the -pleated
sheet structure.

Tertiary Structure

The tertiary structure of a polypeptide chain is its overall three-dimensional shape, once
all the secondary structure elements have folded together among each other. Interactions
between polar, nonpolar, acidic, and basic R group within the polypeptide chain create
the complex three-dimensional tertiary structure of a protein. When protein folding takes
place in the aqueous environment of the body, the hydrophobic R groups of nonpolar
amino acids mostly lie in the interior of the protein, while the hydrophilic R groups lie
mostly on the outside. Cysteine side chains form disulfide linkages in the presence of
oxygen, the only covalent bond forming during protein folding. All of these interactions,
weak and strong, determine the final three-dimensional shape of the protein. When a
protein loses its three-dimensional shape, it will no longer be functional.
 Tertiary structure: The tertiary structure of proteins is determined by hydrophobic interactions, ionic bonding,
hydrogen bonding, and disulfide linkages.

Quaternary Structure

The quaternary structure of a protein is how its subunits are oriented and arranged with
respect to one another. As a result, quaternary structure only applies to multi-subunit
proteins; that is, proteins made from more than one polypeptide chain. Proteins made
from a single polypeptide will not have a quaternary structure.

In proteins with more than one subunit, weak interactions between the subunits help to
stabilize the overall structure. Enzymes often play key roles in bonding subunits to form
the final, functioning protein.

For example, insulin is a ball-shaped, globular protein that contains both hydrogen bonds
and disulfide bonds that hold its two polypeptide chains together. Silk is a fibrous protein
that results from hydrogen bonding between different -pleated chains.

Four levels of protein structure: The four levels of protein structure can be observed in these illustrations.

Denaturation and Protein Folding

Denaturation is a process in which proteins lose their shape and, therefore, their function
because of changes in pH or temperature.
 LEARNING OBJECTIVES

Discuss the process of protein denaturation

KEY TAKEAWAYS

Key Points

Proteins change their shape when exposed to different pH or temperatures.

The body strictly regulates pH and temperature to prevent proteins such as
enzymes from denaturing.
Some proteins can refold after denaturation while others cannot.
Chaperone proteins help some proteins fold into the correct shape.
Key Terms

chaperonin: proteins that provide favorable conditions for the correct folding of
other proteins, thus preventing aggregation
denaturation: the change of folding structure of a protein (and thus of physical
properties) caused by heating, changes in pH, or exposure to certain chemicals

Each protein has its own unique sequence of amino acids and the interactions between
these amino acids create a specify shape. This shape determines the proteins function,
from digesting protein in the stomach to carrying oxygen in the blood.

Changing the Shape of a Protein

If the protein is subject to changes in temperature, pH, or exposure to chemicals, the

internal interactions between the proteins amino acids can be altered, which in turn may
alter the shape of the protein. Although the amino acid sequence (also known as the
proteins primary structure) does not change, the proteins shape may change so much
that it becomes dysfunctional, in which case the protein is considered denatured. Pepsin,
the enzyme that breaks down protein in the stomach, only operates at a very low pH. At
higher pHs pepsins conformation, the way its polypeptide chain is folded up in three
dimensions, begins to change. The stomach maintains a very low pH to ensure that
pepsin continues to digest protein and does not denature.

Enzymes

Because almost all biochemical reactions require enzymes, and because almost all
enzymes only work optimally within relatively narrow temperature and pH ranges, many
homeostatic mechanisms regulate appropriate temperatures and pH so that the enzymes
can maintain the shape of their active site.

Reversing Denaturation

It is often possible to reverse denaturation because the primary structure of the

polypeptide, the covalent bonds holding the amino acids in their correct sequence, is
intact. Once the denaturing agent is removed, the original interactions between amino
acids return the protein to its original conformation and it can resume its function.
However, denaturation can be irreversible in extreme situations, like frying an egg. The
heat from a pan denatures the albumin protein in the liquid egg white and it becomes
insoluble. The protein in meat also denatures and becomes firm when cooked.

Denaturing a protein is occasionally irreversible: (Top) The protein albumin in raw and cooked egg white.
(Bottom) A paperclip analogy visualizes the process: when cross-linked, paperclips (amino acids) no longer move
freely; their structure is rearranged and denatured.
Chaperone proteins (or chaperonins ) are helper proteins that provide favorable conditions for protein folding to
take place. The chaperonins clump around the forming protein and prevent other polypeptide chains from
aggregating. Once the target protein folds, the chaperonins disassociate.
Nucleic acids
DNA and RNA structure and function. Nucleotides and polynucleotides. mRNA, rRNA, tRNA, miRNA, and siRNA.
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Introduction
Nucleic acids, and DNA in particular, are key macromolecules for the continuity of life. DNA bears the hereditary information
thats passed on from parents to children, providing instructions for how (and when) to make the many proteins needed to
build and maintain functioning cells, tissues, and organisms.
How DNA carries this information, and how it is put into action by cells and organisms, is complex, fascinating, and fairly mind-
blowing, and well explore it in more detail in the section on molecular biology. Here, well just take a quick look at nucleic acids
from the macromolecule perspective.
Roles of DNA and RNA in cells
Nucleic acids, macromolecules made out of units called nucleotides, come in two naturally occurring
varieties: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is the genetic material found in living organisms, all the
way from single-celled bacteria to multicellular mammals like you and me. Some viruses use RNA, not DNA, as their genetic
material, but arent technically considered to be alive (since they cannot reproduce without help from a host).
DNA in cells
In eukaryotes, such as plants and animals, DNA is found in the nucleus, a specialized, membrane-bound vault in the cell, as well
as in certain other types of organelles (such as mitochondria and the chloroplasts of plants). In prokaryotes, such as bacteria,
the DNA is not enclosed in a membranous envelope, although it's located in a specialized cell region called the nucleoid.
In eukaryotes, DNA is typically broken up into a number of very long, linear pieces called chromosomes, while in prokaryotes
such as bacteria, chromosomes are much smaller and often circular (ring-shaped). A chromosome may contain tens of
thousands of genes, each providing instructions on how to make a particular product needed by the cell.
From DNA to RNA to proteins
Many genes encode protein products, meaning that they specify the sequence of amino acids used to build a particular
protein. Before this information can be used for protein synthesis, however, an RNA copy (transcript) of the gene must first be
made. This type of RNA is called a messenger RNA (mRNA), as it serves as a messenger between DNA and the ribosomes,
molecular machines that read mRNA sequences and use them to build proteins. This progression from DNA to RNA to protein is
called the central dogma of molecular biology.
Importantly, not all genes encode protein products. For instance, some genes specify ribosomal RNAs (rRNAs), which serve as
structural components of ribosomes, or transfer RNAs (tRNAs), cloverleaf-shaped RNA molecules that bring amino acids to the
ribosome for protein synthesis. Still other RNA molecules, such as tiny microRNAs (miRNAs), act as regulators of other genes,
and new types of non-protein-coding RNAs are being discovered all the time.
Nucleotides
DNA and RNA are polymers (in the case of DNA, often very long polymers), and are made up of monomers known
as nucleotides. When these monomers combine, the resulting chain is called a polynucleotide (poly- = "many").
Each nucleotide is made up of three parts: a nitrogen-containing ring structure called a nitrogenous base, a five-carbon sugar,
and at least one phosphate group. The sugar molecule has a central position in the nucleotide, with the base attached to one of
its carbons and the phosphate group (or groups) attached to another. Lets look at each part of a nucleotide in turn.

Image of the components of DNA and RNA, including the sugar (deoxyribose or ribose), phosphate group, and nitrogenous
base. Bases include the pyrimidine bases (cytosine, thymine in DNA, and uracil in RNA, one ring) and the purine bases (adenine
and guanine, two rings). The phosphate group is attached to the 5' carbon. The 2' carbon bears a hydroxyl group in ribose, but
no hydroxyl (just hydrogen) in deoxyribose.
Image modified from "Nucleic acids: Figure 1," by OpenStax College, Biology (CC BY 3.0).
Nitrogenous bases
The nitrogenous bases of nucleotides are organic (carbon-based) molecules made up of nitrogen-containing ring structures.
[Why is it called a base?]
^+start superscript, plus, end superscript
Each nucleotide in DNA contains one of four possible nitrogenous bases: adenine (A), guanine (G) cytosine (C), and thymine (T).
Adenine and guanine are purines, meaning that their structures contain two fused carbon-nitrogen rings. Cytosine and
thymine, in contrast, are pyrimidines and have a single carbon-nitrogen ring. RNA nucleotides may also bear adenine, guanine
and cytosine bases, but instead of thymine they have another pyrimidine base called uracil (U). As shown in the figure above,
each base has a unique structure, with its own set of functional groups attached to the ring structure.
In molecular biology shorthand, the nitrogenous bases are often just referred to by their one-letter symbols, A, T, G, C, and U.
DNA contains A, T, G, and C, while RNA contains A, U, G, and C (that is, U is swapped in for T).
Sugars
In addition to having slightly different sets of bases, DNA and RNA nucleotides also have slightly different sugars. The five-
carbon sugar in DNA is called deoxyribose, while in RNA, the sugar is ribose. These two are very similar in structure, with just
one difference: the second carbon of ribose bears a hydroxyl group, while the equivalent carbon of deoxyribose has a hydrogen
instead. The carbon atoms of a nucleotides sugar molecule are numbered as 1, 2, 3, 4, and 5 (1 is read as one prime), as
shown in the figure above. In a nucleotide, the sugar occupies a central position, with the base attached to its 1 carbon and the
phosphate group (or groups) attached to its 5 carbon.
Phosphate
Nucleotides may have a single phosphate group, or a chain of up to three phosphate groups, attached to the 5 carbon of the
sugar. Some chemistry sources use the term nucleotide only for the single-phosphate case, but in molecular biology, the
broader definition is generally accepted^11start superscript, 1, end superscript
In a cell, a nucleotide about to be added to the end of a polynucleotide chain will bear a series of three phosphate groups.
When the nucleotide joins the growing DNA or RNA chain, it loses two phosphate groups. So, in a chain of DNA or RNA, each
nucleotide has just one phosphate group.
Polynucleotide chains
A consequence of the structure of nucleotides is that a polynucleotide chain has directionality that is, it has two ends that
are different from each other. At the 5 end, or beginning, of the chain, the 5 phosphate group of the first nucleotide in the
chain sticks out. At the other end, called the 3 end, the 3 hydroxyl of the last nucleotide added to the chain is exposed. DNA
sequences are usually written in the 5' to 3' direction, meaning that the nucleotide at the 5' end comes first and the nucleotide
at the 3' end comes last.
As new nucleotides are added to a strand of DNA or RNA, the strand grows at its 3 end, with the 5 phosphate of an incoming
nucleotide attaching to the hydroxyl group at the 3 end of the chain. This makes a chain with each sugar joined to its neighbors
by a set of bonds called a phosphodiester linkage.
Properties of DNA
Deoxyribonucleic acid, or DNA, chains are typically found in a double helix, a structure in which two matching (complementary)
chains are stuck together, as shown in the diagram at left. The sugars and phosphates lie on the outside of the helix, forming
the backbone of the DNA; this portion of the molecule is sometimes called the sugar-phosphate backbone. The nitrogenous
bases extend into the interior, like the steps of a staircase, in pairs; the bases of a pair are bound to each other by hydrogen
bonds.

Structural model of a DNA double helix.

Image credit: Jerome Walker/Dennis Myts.
The two strands of the helix run in opposite directions, meaning that the 5 end of one strand is paired up with the 3 end of its
matching strand. (This is referred to as antiparallel orientation and is important for the copying of DNA.)
So, can any two bases decide to get together and form a pair in the double helix? The answer is a definite no. Because of the
sizes and functional groups of the bases, base pairing is highly specific: A can only pair with T, and G can only pair with C, as
shown below. This means that the two strands of a DNA double helix have a very predictable relationship to each other.
For instance, if you know that the sequence of one strand is 5-AATTGGCC-3, the complementary strand must have the
sequence 3-TTAACCGG-5. This allows each base to match up with its partner:
5'-AATTGGCC-3' 3'-TTAACCGG-5'
These two strands are complementary, with each base in one sticking to its partner on the other. The A-T pairs are connected
by two hydrogen bonds, while the G-C pairs are connected by three hydrogen bonds.
When two DNA sequences match in this way, such that they can stick to each other in an antiparallel fashion and form a helix,
they are said to be complementary.

Hydrogen bonding between complementary bases holds DNA strands together in a double helix of antiparallel strands.
Thymine forms two hydrogen bonds with adenine, and guanine forms three hydrogen bonds with cytosine.
Image modified from OpenStax Biology.
Properties of RNA
Ribonucleic acid (RNA), unlike DNA, is usually single-stranded. A nucleotide in an RNA chain will contain ribose (the five-carbon
sugar), one of the four nitrogenous bases (A, U, G, or C), and a phosphate group. Here, we'll take a look at four major types of
RNA: messenger RNA (mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), and regulatory RNAs.
Messenger RNA (mRNA)
Messenger RNA (mRNA) is an intermediate between a protein-coding gene and its protein product. If a cell needs to make a
particular protein, the gene encoding the protein will be turned on, meaning an RNA-polymerizing enzyme will come and
make an RNA copy, or transcript, of the genes DNA sequence. The transcript carries the same information as the DNA
sequence of its gene. However, in the RNA molecule, the base T is replaced with U. For instance, if a DNA coding strand has the
sequence 5-AATTGCGC-3, the sequence of the corresponding RNA will be 5-AAUUGCGC-3.
Once an mRNA has been produced, it will associate with a ribosome, a molecular machine that specializes in assembling
proteins out of amino acids. The ribosome uses the information in the mRNA to make a protein of a specific sequence, reading
out the mRNAs nucleotides in groups of three (called codons) and adding a particular amino acid for each codon.
Image of a ribosome (made of proteins and rRNA) bound to an mRNA, with tRNAs bringing amino acids to be added to the
growing chain. The tRNA that binds, and thus the amino acid that's added, at a given moment is determined by the sequence
of the mRNA that is being "read" at that time.
Image credit: OpenStax Biology.
Ribosomal RNA (rRNA) and transfer RNA (tRNA)
Ribosomal RNA (rRNA) is a major component of ribosomes, where it helps mRNA bind in the right spot so its sequence
information can be read out. Some rRNAs also act as enzymes, meaning that they help accelerate (catalyze) chemical reactions
in this case, the formation of bonds that link amino acids to form a protein. RNAs that act as enzymes are known
as ribozymes.
Transfer RNAs (tRNAs) are also involved in protein synthesis, but their job is to act as carriers to bring amino acids to the
ribosome, ensuring that the amino acid added to the chain is the one specified by the mRNA. Transfer RNAs consist of a single
strand of RNA, but this strand has complementary segments that stick together to make double-stranded regions. This base-
pairing creates a complex 3D structure important to the function of the molecule.

Structure of a tRNA. The overall molecule has a shape somewhat like an L.

Image modified from Protein Data Bank (work of the U.S. government).
Regulatory RNA (miRNAs and siRNAs)
Some types of non-coding RNAs (RNAs that do not encode proteins) help regulate the expression of other genes. Such RNAs
may be called regulatory RNAs. For example, microRNAs (miRNAs) and small interfering RNAs siRNAsare small regulatory RNA
molecules about 22 nucleotides long. They bind to specific mRNA molecules (with partly or fully complementary sequences)
and reduce their stability or interfere with their translation, providing a way for the cell to decrease or fine-tune levels of these
mRNAs.
These are just some examples out of many types of noncoding and regulatory RNAs. Scientists are still discovering new varieties
of noncoding RNA.
[More about regulatory RNAs]
^2start superscript, 2, end superscript
Summary: Features of DNA and RNA
DNA RNA
Repository of genetic Involved in protein synthesis and gene regulation; carrier of genetic information
Function information in some viruses
Sugar Deoxyribose Ribose
Structure Double helix Usually single-stranded
Bases C, T, A, G C, U, A, G
------------------------------------------------------------------------
Nucleic Acids & DNA
Remember: Phosphate, Base, Pentose Sugar!
Nucleic acids such as DNA or RNA are made up from nucleotides. These nucleotides are made of three parts, a phosphate (or
phosphoric acid H3PO4), organic base and a pentose sugar.
The Phosphate part of a nucleic acid has the same regular structure for any nucleic acid. The organic base can be once of five
different bases. The pyrimidine bases are thymine, cytosine and uracil. The Purine bases are adenine and guanine. There are also
two different types of pentose sugar which differ between DNA and RNA, the pentose sugar in DNA is deoxyribose and in RNA
it is ribose.
Shown below is a simplified diagram of a nucleotide.
And again below this is a full diagram of a nucleotide. You can see the separate parts, the phosphate molecule which is linked
with the pentose sugar by a condensation reaction. You can also see the hydrogen bond between the pentose sugar and the
organic base.
Deoxyribonucleic Acid (DNA)
DNA is a double stranded polymer in the form of a double helix.
It may be made up from millions of nucleotides.
Pentose Sugar: deoxyribose
Choice of four organic bases, adenine, guanine, cytosine and thymine. They pair up, cytosine with guanine and adenine with
thymine.
DNA has two main functions, replication when the cell divides and to carry information during protein synthesis.
Ribonucleic Acid (RNA)
RNA is different to DNA in the fact that it is a single stranded polymer rather than a helix.
Pentose Sugar: Ribose
Choice of four organic bases, adenine, guanine, cytosine and uracil (mainpoint: not thymine). They also pair up, cytosine with
guanine and adenine with uracil.
Three types of RNA, ribosomal (rRNA), transfer (tRNA) and messenger (mRNA).
DNA Replication
When cells divide the daughter cell must receive an exact copy of the genetic material from the parent.
DNA replicates by unwinding into separate strands with help from DNA polymerase which adds free nucleotides to the exposed
bases.
Each chain acts as a template for free nucleotides so that they can be joined to their complementary bases.
The result is that there are two DNA molecules, each with one new synthesised strand of DNA and one strand from the original.

An example of this would be with the bacteria Escherichia coli and with different isotopes of Nitrogen. The bacteria was
exposed to N15 for several generations until it was exposed to a lighter N14. Scientists could then distinguish between the
different DNA densities by centrifuging them.
Protein synthesis
Protein synthesis can be slit up into five main stages:
The DNA helix unzips itself and RNA polymerase makes an exact copy of the DNA strand in the form of mRNA. This process is
called transcription.
The mRNA moves out of the nucleus via a nuclear pore and goes to a ribosome. A codon is made up from three organic bases
and these are what code for specific amino acids.
The mRNA lines up on a ribosome, which has two tRNA binding sites, one binding site is for a tRNA to bind with the
polypeptide being formed, the other binding site is for a tRNA and new amino acids.
Each codon is read in turn and a chain of amino acids is formed with peptide bonds (via a condensation reaction).
Once the last codon (stop codon) is reached then the protein is formed.