Molecular Biology: Protein Structure and Functions - Stepanov V.M. 2005

Secondary Structure
α-Helix

In the 1950s, L. Pauling and R. Corey, drawing on data regarding the crystal structures of Amino Acids and simple Peptides, examined potential periodic Conformations of the polypeptide chain and concluded that the most probable Structure was the one they designated as the a-helix. Their Selection of this specific Secondary structure was based on the following criteria:

1. Formation of a closely packed, compact structure devoid of voids and atomic overlaps.

2. Maximum saturation of the structure with Hydrogen Bonds, under the condition that the geometry of the O ∙∙∙ H ∙∙∙ N Hydrogen bond is close to linear.

3. Preservation of the interatomic distances and Bond Angles characteristic of amino acids and simple peptides.

Adhering to these conditions allows for the construction of both right-handed and left-handed a-helices; however, the right-handed a-helix (Fig. 5.5) proves to be somewhat more energetically favorable than the left-handed one when the peptide chain is composed of L-amino acids. On the Ramachandran map, the left-handed a-helix corresponds to a small depression with dihedral angles of φ = +57° and ψ = +47°.

Class="center">

Fig. 5.5. Right-handed a-helix. A — showing only C_a atoms; B — all atoms of the peptide chain backbone; C — more complete structure.

The peptide chain (from the N- to the C-terminal residue) runs from top to bottom. Hydrogen bonds connect the carbonyl oxygen of the i-th residue to the hydrogen of the NH group of the (i+4)-th residue. Side chains of amino acids separated by two or three residues lie in close spatial proximity. The atoms within the helix appear widely spaced only because they are depicted at a reduced scale for clarity. Taking into account the actual Van der Waals radii of the atoms, the a-helix represents a densely packed structure lacking an internal channel and impermeable even to Water. Projected onto the helical axis, the distance between adjacent C_a atoms is 1.5 A, the rotation angle per residue is 100°, and a full turn of the helix (360°) encompasses 3.6 residues.

The theoretical deductions made by Pauling and Corey were subsequently fully validated. The a-helix indeed represents one of the primary, albeit not the only, types of secondary structure.

The a-helix is characterized by the following parameters. The theoretically predicted dihedral angles are φ = -58° and ψ = -41°; the average values derived from X-ray crystallographic analysis of 57 Proteins are φ = -62° and ψ = -41°. Its radius is 2.3 Ź, the rise per amino acid residue along the helix axis is 1.5 A, the average number of residues per turn is 3.6, and the pitch of the helix (i.e., the vertical distance the peptide chain rises per single turn) is 5.4 Å. All carbonyl groups in the a-helix are oriented in the same direction—forward along the path of the peptide chain from the amino end to the carboxyl end—while the N—H groups point backward.

Hydrogen bonds are established between the C=O and N—H groups (Fig. 5.5) such that the carbonyl group of the i-th residue forms a bond with the N—H group of the (i+4)-th residue, the carbonyl group of the (i+1)-th residue with the N—H group of the (i+5)-th residue, and so forth. The fact that the NH group, rather than the carbonyl of the (i+4)-th residue, is positioned "above" the carbonyl group of the i-th residue corresponds precisely to the 3.6 residues per helical turn.

Every peptide group is polarized and characterized by a specific dipole moment, with the negative charge concentrated on the carbonyl oxygen and the positive charge on the nitrogen atom. Because the peptide groups are unidirectionally oriented within the a-helix, their dipole moments reinforce one another, imparting a net dipole moment to the a-helix as a whole. Consequently, partial negative and positive charges accumulate at its respective ends, which can play a crucial functional role within the protein.

The capacity for hydrogen bond formation between peptide groups in the a-helix is fully utilized. In this sense, the a-helix is saturated and internally closed. Unlike the ß-Structure, it is incapable of interacting with other elements of secondary structure through The formation of inter-peptide hydrogen bonds.

Non-covalent contacts involving the side chains of the amino acids comprising the a-helix play a vital role in establishing the Spatial Structure of the protein. Crucially, the side chains of amino acids separated by two or three residues in the peptide chain are brought into close proximity On the surface of the a-helix. When these positions are occupied by hydrophobic amino acids, they form a distinct hydrophobic ridge. The interaction between such ridges serves as a mechanism for packing a-helices within the Tertiary Structure of a protein. Hydrophilic, particularly charged, surfaces can be formed in an identical manner. Consequently, an a-helix may be purely hydrophobic, which is characteristic of transmembrane protein segments, or amphiphilic—possessing both hydrophobic and hydrophilic faces (Fig. 5.6).

1 1Å = 0.1 nm.

Fig. 5.6. Distribution of hydrophilic and hydrophobic amino acids on The surface of one of the a-helices of apolipoprotein C-I. A — hydrophilic surface; B — Hydrophobic surface, clearly displaying the ridge formed (from bottom to top) by the side chains of leucine, valine, two phenylalanine residues, Methionine, and another leucine.

The length of a-helical segments in Globular proteins is relatively short, typically spanning 5–15 amino acid residues and rarely exceeding 3–4 helical turns; in Fibrous proteins, they are considerably more extended. Kinks in the a-helix are occasionally observed, typically at sites where Proline residues are incorporated, which disrupt the hydrogen-bonding network. At these points, the axis of the helix is deflected by 20–30°.