Secondary structure and backbone conformation:part 2:The alpha-helix

Development of an a-helix structure model:

Pauling and Corey twisted models of polypeptides around to find ways of getting the backbone into regular conformations which would agree with a-keratin fibre diffraction data. The most simple and elegant arrangement is a right-handed spiral conformation known as the 'a-helix'.

An easy way to remember how a right-handed helix differs from a left-handed one is to hold both your hands in front of you with your thumbs pointing up and your fingers curled towards you. For each hand the thumbs indicate the direction of translation and the fingers indicate the direction of rotation.

 Properties of the a-helix:

The structure repeats itself every 5.4 Å along the helix axis, i.e. we say that the a-helix has a pitch of 5.4 Å. a-helices have 3.6 amino acid residues per turn, i.e. a helix 36 amino acids long would form 10 turns. The separation of residues along the helix axis is 5.4/3.6 or 1.5 Å, i.e. the a-helix has a rise per residue of 1.5 Å.

1. Every main chain C=O and N-H group is hydrogen-bonded to a peptide bond 4 residues away (i.e. O_i to N_i+4). This gives a very regular, stable arrangement.
2. The peptide planes are roughly parallel with the helix axis and the dipoles within the helix are aligned, i.e. all C=O groups point in the same direction and all N-H groups point the other way. Side chains point outward from helix axis and are generally oriented towards its amino-terminal end.

All the amino acids have negative phi and psi angles, typical values being -60 degrees and -50 degrees, respectively.

Distortions of a-helices:

The majority of a-helices in globular proteins are curved or distorted somewhat compared with the standard Pauling-Corey model. These distortions arise from several factors including:

1. The packing of buried helices against other secondary structure elements in the core of the protein.
2. Proline residues induce distortions of around 20 degrees in the direction of the helix axis. This is because proline cannot form a regular a-helix due to steric hindrance arising from its cyclic side chain which also blocks the main chain N atom and chemically prevents it forming a hydrogen bond. Janet Thornton has shown that proline causes two H-bonds in the helix to be broken since the NH group of the following residue is also prevented from forming a good hydrogen bond. Helices containing proline are usually long perhaps because shorter helices would be destabilised by the presence of a proline residue too much. Proline occurs more commonly in extended regions of polypeptide.
3. Solvent. Exposed helices are often bent away from the solvent region. This is because the exposed C=O groups tend to point towards solvent to maximise their H-bonding capacity, i.e. tend to form H-bonds to solvent as well as N-H groups. This gives rise to a bend in the helix axis.

1. 3₁₀-Helices. Strictly, these form a distinct class of helix but they are always short and frequently occur at the termini of regular a-helices. The name 3₁₀ arises because there are three residues per turn and ten atoms enclosed in a ring formed by each hydrogen bond (note the hydrogen atom is included in this count). There are main chain hydrogen bonds between residues separated by three residues along the chain (i.e. O_i to N_i+3). In this nomenclature the Pauling-Coreya-helix is a 3.6₁₃-helix. The dipoles of the 3₁₀-helix are not so well aligned as in the a-helix, i.e. it is a less stable structure and side chain packing is less favourable.

Courtesy: swissmodel expasy