III.

Proteins and Polypeptides

A. Amino Acids of
Different Polarity
are Joined Together
to Form Linear
Polymers.
1) Polarity of different R groups

2) A peptide bond is formed in a dehydration reaction that

joins two amino acids together (and several to many in a
polypeptide).

Note the aminocarboxy polarity of the

peptide bond and the
entire polypeptide.
While the amide bond forms a plane, the
bonds that contain the C carbon can rotate,
allowing polypeptides to adopt different
conformations in space.

3) mRNAs are translated into proteins.

Codons for each

amino acid are
3 nucleotides
long and
arranged
sequentially

4) Polypeptides are synthesized in the N-terminal to Cterminal direction.

N-terminus

C-terminus

Which of the following is (are) differences between DNA and

RNA?
A. DNA contains the sugar deoxyribose, while
RNA contains the sugar ribose.
B. DNA contains the base uracil, while RNA
contains the base thymine.
C. RNA contains the base uracil, while DNA
contains the base thymine.
D. The bases in RNA never form hydrogen
bonds with other nucleic acid bases.
E. A and B are both true.
F. A and C are both true.

Below is shown a peptide bond (in yellow). Tell me which bond

points away from this bond towards the amino (NH2) terminus of
the polypeptide containing these bonds (i.e., which bond is the
most amino terminal?).
A.
B.
C.
D.
E.

A.
B.
C.
D.
There is no way to tell

5) Proteins are amino acid polymers that possess three

important traits.

An enzyme binds a substrate

at its active site to catalyze a
biochemical reaction

low
Evolution gets rid
of these.

B. Protein Structure is Classified into Four

Categories.
1) Primary Structure is defined by the linear sequence of
amino acids.

2) Secondary Structure is defined by regions of repetitive,

predictable organization in the primary structure: -helix, sheet and random coil

a. An -helix is shaped like a coil, with R groups projecting away from

the coil towards the outside.

3.6 amino
acids per
turn;
backbone
carbonyls
and amino
groups
hydrogen
bond.
Right-handed helix

b. A -sheet forms a pleated plane via hydrogen bonding between the

carbonyl and amino groups in the polypeptide backbone.
Strands of the sheet are separated
by loops of varying lengths.

R-groups alternate
on opposite sides
of the sheet.

A difference between -helices and sheets is that

A. Within -helices, every carbonyl oxygen and amino
hydrogen in the peptide backbone is involved in a
hydrogen bond, while in -sheet regions only every
other carbonyl oxygen and amino hydrogen are
involved in hydrogen bonds.
B. Within -helices but not within -sheet regions, every
hydrogen bond occurs between atoms separated by
a fixed distance in the polypeptide sequence.
C. WithIn -sheet regions but not within -helices, every
R group projects on the same side of the secondary
structure.
D. All of the above (A, B, and C) are true.

3) Tertiary Structure is defined by the arrangement of the

secondary structures in three dimensions.
a. Sometimes protein folding is facilitated by chaperonins

b. Other proteins can fold spontaneously without the involvement of

other proteins.

c) Three dimensional structures can be depicted in several ways.

d. Many proteins are classified by their type of tertiary structure (e.g.,

globular, filamentous or transmembrane

e. The primary structure (i.e., amino acid sequence) of the polypeptide chain
determines its secondary (local) structure (e.g., helix, sheet), and
secondary elements fold to form domains that give the protein tertiary
structure (i.e., three dimensional structure).
A domain is a segment of a
polypeptide chain that can fold into a
stable structure.
-modular unit of structure
-may have specific function

Blue domain binds

the small molecule
cAMP

Catabolite
activator
protein (CAP)
Grey domain binds
DNA when blue
domain binds cAMP,
because it changes
conformation.

f. Many proteins also contain unstructured regions that serve several

different functions.

4) Quaternary structure is defined by the 3-D arrangement of

polypeptide subunits in multimeric proteins (e.g., the antibody protein
tetramer two heavy and two light chains).

Protein folding is like a game of Twister arranging the

conformation of the polypeptide to maximize the number of
productive contacts

5) Five classes of chemical bonds (mostly noncovalent)

stabilize protein structure, determined by all the interatomic
interactions between R groups.
Covalent, from cysteines

Hydrophobic side chains move

away from water and cluster in the
interior of proteins

Enzymes must bind their substrates (the reactants, which are

ligands) only transiently, often with such noncovalent bonds, in a
manner that allows chemical bonds to be broken and reformed.
Transition state

Active site

This can involve the transient formation of covalent bonds between the
enzyme and substrate(s). The bonds are transient because the enzyme
must be left in its original state to catalyze multiple rounds of the reaction
step.

C. Changing Protein Shape and Protein

Function
1) Proteins change their shape in response to changes in
their environment.
a. Detergents (e.g., soaps) can disrupt hydrophobic bonds
b. Increased temperature destabilizes proteins (proteins vibrate
more, so noncovalent bonds cannot hold them together)
c. Increased ions (e.g., Na+ of Cl-) can displace similarly charged
amino acids in the 3-D structure
d. pH (amount of protons in solution) changes can alter charge
state of charged amino acids

2) Cells chemically modify proteins to control their shape

and function.
a. Covalent modifications are relatively long-lasting.
Proteins located at
cell surface or
extracellular space

Tethers proteins to
membranes

Marks proteins for

degradation

Regulation of
transcription

Negative charge modifies interactions/conformation

b. Allosteric binding of small molecule regulators like ATP, GTP or Ca ++

that cause changes in the conformation of the protein.

-How are proteins controlled, so that cells can turn their functioning on or off as
needed, so that not too much or too little products are made?
In feedback inhibition, an enzyme working early in a pathway is
inhibited (turned off) by a late product of the pathway.

The late product typically inhibits the early enzyme by binding to it. Since
the late product has a very different structure from the substrate for the
enzyme, it must bind the enzyme at a different site from the active site.
Aspartate transcarbamoylase begins the synthesis of C, U and T bases

The regulator affects the active site by causing a conformational

change in the protein when it binds.
Regulation of this sort is termed allosteric and can be positive or negative
in nature.

If a protein contains a primary binding site and an allosteric

site, what else can you predict about this protein?
A. The primary binding site has a higher concentration
of hydrophobic amino acids than the allosteric site.
B. The protein has quaternary structure.
C. The primary binding site and the allosteric site form a
domain.
D. The primary binding site contains alpha helices
and/or beta sheets, but the allosteric site does not.
E. Occupancy of the allosteric site alters the binding
affinity of the primary site.

-GTP is a regulator that binds GTP-binding-proteins to activate them.

The activation of these proteins can be regulated by the binding of

another protein to the G protein; this protein speeds the release of
GDP, so that GTP can bind again.
The G protein eventually inactivates itself by hydrolyzing the bound
GTP.
GTP-binding proteins bind GTP they do not phosphorylate GDP to
produce GTP

3) Proteins are classified into nine categories according to

their function.
a. Enzymes catalyze chemical reactions.
b. Regulatory proteins control activities of enzymes.
c. Structural proteins form stable complexes inside cells to provide
support.
d. Motility proteins interact with structural proteins to generate motion.
e. Transport proteins move molecules across membranes
f. Hormonal proteins are chemical signals between cells.
g. Receptor proteins receive and transmit signals to which they bind.
h. Defensive proteins (e.g., antibodies) target and neutralize harmful
molecules
i. Storage proteins bind to and protect energy sources from

D. Degradation of Proteins that have Stopped

Functioning (Worn-out Proteins) without
Destruction of All Proteins (Cell Death).
1) Proteins in the cytosol and nucleus are broken down by
the proteasome, a large capped multiprotein barrel.
Cleavage of the peptide bond

2) Proteins in organelles (soluble and membrane-bound) are

digested in lysosomes.

3) Proteins in the extracellular space are digested by

secreted proteinases that are antagonized by protease
inhibitors.

The covalent modification that targets

proteins to the proteasome is
A. Phosphate
B. Acetyl group
C. Ubiquitin
D. Binding of GTP
E. All of the above always
function in this manner.