Structure of Proteins (continued)
Functional proteins have a 3-D shape --- stretched out protein is not functional. Function arises from the 3-dimensional shape which is predetemined by the sequence of amino acids that make up a protein. So how is protein structure determined?
1. The peptide (or amide) bond is rigid-but the (alpha-carbon and its R-group can freely rotate.
2. Polypeptides can fold into (alpha-helix or beta-pleated sheet forms which were predicted by Pauling 6 years before he proved that they actually existed.
alpha-helix. The (alpha-helix is stabilized by extensive hydrogen bonding between the carbonyl oxygen of one amino acid and the NH of another amino acid. As shown in the transparency, the amino acids of an alpha-helix align themselves along a right-handed thread-like chain. The rise and degree of rotation are shown. Notice that amino acids which are 3 to 4 units apart in the linear sequence are actually close together in an alpha-helix. Amino acids which are adjacent to each other in sequence are actually far apart.
The alpha-helical content of proteins ranges from virtually none to 100%. Chymotrypsin, a protease, is devoid of helix, while hemoglobin contains roughly 75%. Two or more (alpha-helices can entwine to form very long and rigid coils such as found in myosin in muscle, fibrin in blood clots, and keratin in hair.
Beta-Pleated sheets. This structure is radically different from the helix. Rather than the tightly coiled nature of the (alpha-helix, the beta-pleated sheet is almost fully extended and flat. This structure is also stablized by H-bonding but the bonding is between different strands of protein, whereas in the alpha-helix all H-bonding is between residues in the same strand. A noteworthy example of a protein which is completely composed of B-sheet structure is silk protein.
Reverse turns. Most proteins are very compact because of the many turns in the direction of the peptide chain. Here, the carbonyl of one amino acid H-bonds to the amide nitrogen of an amino acid 3 residues away (w/ resp. to the linear sequence).
A special helix-collagen. Collagen is the most abundant protein of mammals. It is the principal component of skin, bone, tendon, cartilage, and teeth. The extracellular protein is composed of three helical chains, each nearly 1000 residues long with a very regular sequence -- Nearly every third amino acid residue is glycine! Proline and hydroxyproline (a rare amino acid) are present in abundance; the sequence: glycine-proline- hydroxyproline, recurs frequently in the sequence. Why?
Proline and hydroxyproline have relatively large and bulky side chains which repel each other by shear steric hindrance (recall that collagen is a twisting mesh of three proteins). Thus, there is no room for anything other than a hydrogen to exist in the third position (hence-glycine). What happens if there is a mutation in a single glycine coding region?
What forces determine the 3-D structure of proteins? Electrostatic interactions, hydrogen bonds, Van der Walls forces -- all of which are brought about by the amino acid sequence of the protein.
Four Basic Levels of Structure in Protein Architecture.
Primary structure Predetermines 3 D shape: Anfinsen experiment.
You might then ask if the 3D shape of a protein can be deduced from the primary sequence? Answer: We're getting much better at it.
Allosterism is briefly introduced in this chapter but I choose to leave it out for now ... until we focus our attention on hemoglobin and myoglobin.