Question

From an examination of the structure of the a-helix, why is it impossible to have both L- and D- amino acids in the same polypeptide?

Answer 1

Pauling and Corey were aware of the importance of hydrogen bonds in orienting polar chemical groups such as the -C=O and -N-H groups of the peptide bond. They also had the experimental results of William Astbury, who in the 1930s had conducted pioneering x-ray studies of proteins. Astbury demonstrated that the protein that makes up hair and wool (the fibrous protein α-keratin) has a regular structure that repeats every 0.54 nm. With this information and their data on the peptide bond, and with the help of precisely constructed models, Pauling and Corey set out to determine the likely conformations of protein molecules.

The simplest arrangement the polypeptide chain could assume with its rigid peptide bonds (but with the other single bonds free to rotate) is a helical structure, which Pauling and Corey called the α helix (Fig. 7-6). In this structure the polypeptide backbone is tightly wound around the long axis of the molecule, and the R groups of the amino acid residues protrude outward from the helical backbone. The repeating unit is a single turn of the helix, which extends about 0.56 nm along the long axis, corresponding closely to the periodicity

Figure: Four models of the a helix, showing different aspects of its structure. (a) Formation of a right-handed α helix. The planes of the rigid peptide bonds are parallel to the long axis of the helix. (b) Ball-and-stick model of a right-handed α helix, showing the intrachain hydrogen bonds. The repeat unit is a single turn of the helix, 3.6 residues.(c) The α helix as viewed from one end, looking down the longitudinal axis. Note the positions of the R groups, represented by red spheres. (d) A space-filling model of the α helix.

Astbury observed on x-ray analysis of hair keratin. The amino acid residues in an a helix have conformations with ψ = -45°to -50°and φ = -60° and each helical turn includes 3.6 amino acids. The twisting of the helix has a right-handed sense (Box 7-1) in the most common form of the α helix, although a very few left-handed variants have been observed.

The α helix is one of two prominent types of secondary structure in proteins. It is the predominant structure in α-keratins. In globular proteins, about one-fourth of all amino acid residues are found in α helices, the fraction varying greatly from one protein to the next.

ot all polypeptides can form a stable α helix. Additional interactions occur between amino acid side chains that can stabilize or destabilize this structure. For example, if a polypeptide chain has many Glu residues in a long block, this segment of the chain will not form an α helix at pH 7.0. The negatively charged carboxyl groups of adjacent Glu residues repel each other so strongly that they overcome the stabilizing influence of hydrogen bonds on the α helix. For the same reason, if there are many adjacent Lys and/or Arg residues, with positively charged R groups at pH 7.0, they will also repel each other and prevent formation of the α helix. The bulk and shape of certain R groups can also destabilize the α helix or prevent its formation. For example, Asn, Ser, Thr, and Leu residues tend to prevent formation of the α helix if they occur close together in the chain.

The twist of an α helix ensures that critical interactions occur between an amino acid side chain and the side chain three (and sometimes four) residues away on either side of it. Positively charged amino acids are often found three residues away from negatively charged amino acids, permitting the formation of an ionic interaction. Two aromatic amino acids are often similarly spaced, resulting in a hydrophobic interaction.

A minor constraint on the formation of the α helix is the presence of Pro residues. In proline the nitrogen atom is part of a rigid ring , and rotation about the N-C_α bond is not possible. In addition, the nitrogen atom of a Pro residue in peptide linkage has no substituent hydrogen-to-hydrogen bond with other residues. For these reasons, proline is only rarely found within an α helix.

Why does such a helix form more readily than many other possible conformations? The answer is, in part, that it makes optimal use of internal hydrogen bonds. The structure is stabilized by a hydrogen bond between the hydrogen atom attached to the electronegative nitrogen atom of each peptide linkage and the electronegative carbonyl oxygen atom of the fourth amino acid on the amino-terminal side of it in the helix (Fig. 7-6b). Every peptide bond of the chain participates in such hydrogen bonding. Each successive coil of the α helix is held to the adjacent coils by several hydrogen bonds, which in summation give the entire structure considerable stability.

Further model-building experiments have shown that an α helix can form with either L- or D-amino acids. However, all residues must be of one stereoisomeric series; a D-amino acid will disrupt a regular structure consisting of L-amino acids, and vice versa. Naturally occurring L-amino acids can form either right- or left-handed helices, but, with rare exceptions, only right-handed helices are found in proteins.