Proteins

Learning Objectives
Primary, secondary, tertiary, and quaternary structure Structure of collagen, a fibrous protein Location of polar and nonpolar residues in globular proteins Myoglobin Hemoglobin and sickle-cell anemia

Primary Structure
Primary structure of a protein is the amino acid sequence of its polypeptide chain. For example, the primary structure of an antifreeze protein in one-letter code is:
DTASDAAAAAALTAANAKAAAELTAANAAAAAAATAR

A protein has tens to thousands of amino acid residues 100 amino acid residues may be combined in 20100 10130 different sequences (the universe has 1079 atoms) The primary structure determines properties of a protein, while the amino acid composition is relatively not important (compare word atom and its anagram moat) Each protein consists of one ore more polypeptide chains

Protein Structure Levels

Figure 6-1.

Secondary Structure
Secondary structure refers to a spatial arrangement of the backbone without regard to the side chain conformations -Helix. Backbone carbonyl C=O of the residue N accepts H-bond from the backbone N-H group of the residue N+4 (Fig. 6-8).

Secondary Structure
-sheets are stabilized by H-bonds between two parallel backbones. In the parallel -sheet, the backbones extend in the same directions. In the antiparallel sheet, the backbones extend in opposite directions (Fig. 6-9).

Collagen
Depending on their overall shape, proteins are classified as either fibrous or globular. The fibrous protein collagen is the most abundant vertebrate protein. It has numerous Gly, Pro, and hydroxy-Pro residues. Collagen triple-helix fibers are the major stress-bearing components of connective tissues (bone, teeth, tendon) and the fibrous matrices of skin and blood vessels.

Fig. 6-16.

Collagen is a TripleHelix Protein

Side chains of certain Pro residues in collagen are hydroxylated with the help of enzyme prolyl hydroxylase and coenzyme ascorbic acid (vitamin C). Lack of vitamin C results in scurvy (collagen cannot form fibers).

The superhelical structure of collagen is formed of three collectively twisted polypeptide helices

Tertiary Structure
The tertiary structure of a protein refers to the folding of its secondary structure segments. The segments are joined by reverse turns, which usually occur on the surface of the protein. The 3D structures of proteins are studied experimentally by X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and theoretically by molecular modeling. > 20,000 3D structures of proteins are deposited in the Brookhaven Protein Data Bank (http://www.rcsb.org). Freeware program RASMOL may be used to visualize proteins.

Visualization of Proteins
Atoms in proteins are tightly packed. Showing all atoms obscure internal details. Usually, only backbones are visualized. Figure 6-28 -Helices are drawn as ribbons passing via C atoms.

Visualization of Proteins

-Sheets are drawn as flat arrows pointing toward the C-terminus.

Visualization of Proteins
Proportions and arrangements of secondary structure segments vary in different proteins. Unfolding of a protein (denaturation) may require the free energy as small as 0.4 kJ/mol per residue.

Fig. 6-30

Location of Polar and Nonpolar Residues

Hydrophobic residues prevail in the protein interior. Hydrophilic residues prevail at the protein surface. This arrangement maximizes preferable interactions and minimizes non-preferable interactions with water.

Figure 6-27

Myoglobin
Intracellular protein facilitating O2 transport in vertebrate muscle Contains a heme group that coordinates the central Fe (II) atom
Fig. 7-1.

Oxygen binds reversibly to the heme group in the protein

The Heme Group

Four nitrogen atoms (blue balls) coordinate the central Fe(II) atom (yellow ball). Oxygen molecule (red ball) reversibly binds to Fe(II). Toxic compounds such as CO (carbon monoxide) and NO (nitric oxide) bind to the heme group with much higher affinity than O2. Every year, nearly 300 people in the United States die from CO. Oxidation of Fe(II) to Fe(III) converts myoglobin to metmyoglobin. Oxidized forms of myoglobin and hemoglobin are responsible for the brown color of old meat and dried blood

Hemoglobin
Animals > 1 mm thick use circulatory system and oxygenbinding proteins to deliver oxygen to the interior tissues. Hemoglobin, the major component of erythrocytes, transports O2 from the lungs to respiring tissue that returns carbon dioxide (CO2).
In erythrocyte, carbonic anhydrase catalyzes reaction CO2 + H2O H+ + HCO3

Hemoglobin binds bicarbonate (HCO3) and carries it to lung.

Hemoglobin
Figure 7-5

Hemoglobin is a tetramer consisting of two and two subunits. The subunits are similar to each other and to myoglobin. Oxygen binding alters structure of the tetramer

Sickle-Cell Anemia
Hereditary disease caused by the recessive gene of hemoglobin variant in which -chain has Val6 instead of Glu6 in normal hemoglobin.
VHLTPEEKSA... Normal -chain VHLTPVEKSA... Variant -chain

Fig. 7-19

Val6 fit into a hydrophobic pocket on another hemoglobin molecule.

Sickle-Cell Anemia
Hemoglobin molecules polymerize and form fibers that cause erythrocyte deformation

Fig. 7-19

Fig. 7-18