Section 22.2.5.3. Secondary structures

Helices have traditionally been defined in terms of their N—H···O=C hydrogen-bonding patterns as α-helices , 3₁₀-helices , or π-helices ; in an α-helix, for example, the peptide NH of residue 5 hydrogen bonds to the C=O of residue 1. In fact, the vast majority of helices in proteins are α-helices; 3₁₀-helices are rarely more than two turns (six residues) in length, and discrete π-helices have not been seen so far.

The residues within helices have characteristic main-chain torsion angles, (φ, ψ), of around (−63°, −40°) that cause the C=O groups to tilt outwards by about 14° from the helix axis (Baker & Hubbard, 1984). This results in somewhat less linear hydrogen bonding than in the original Pauling model (Pauling et al., 1951), with a degree of distortion towards 3₁₀-helix geometry. Thus, weak interactions are often made in addition to the more favourable hydrogen bonds, giving hydrogen-bond networks that may enhance helix elasticity (Stickle et al., 1992). Tilting outwards also makes the C=O groups more accessible for additional hydrogen bonds from side chains or water molecules. For the α-type, interactions, the hydrogen-bond angles at both donor and acceptor atoms are quite tightly clustered (N—H···O ∼157° and C=O···H ∼147°). The hydrogen-bond lengths in helices average 2.06 (16) Å (O···H) or 2.99 (14) Å (O···N) (Baker & Hubbard, 1984).

Few helices are regular throughout their length. Many are curved or kinked such that one side (often the outer, solvent-exposed side) of the helix is opened up a bit and has longer hydrogen bonds (Blundell et al., 1983; Baker & Hubbard, 1984). The bends are often associated with additional hydrogen bonds from water molecules or side chains to C=O groups that are tilted out more than usual. Curved helices are normal in coiled-coil structures and can enable long helices to pack more effectively in globular structures. Sometimes a kink can be functionally important, as in manganese superoxide dismutase, where a kink in a long helix, incorporating a π-type hydrogen bond, enables the optimal positioning of active-site residues (Edwards et al., 1998).

The beginnings and ends of helices are sites of hydrogen-bonding variations which can be seen as characteristic `termination motifs'. At helix N-termini, 3<sub>10</sub>-type (or bifurcated and ) hydrogen bonds are often found. At C-termini, two common patterns occur. In one, labelled by Baker & Hubbard (1984), there is a transition from α-type, to 3<sub>10</sub>-type, hydrogen bonding, often with genuine bifurcated hydrogen bonds, as in Fig. 22.2.2.1(b), at the transition point. The other, labelled (Baker & Hubbard, 1984) or referred to as the `Schellman motif' (Schellman, 1980), has a π-type, hydrogen bond coupled with a -type, hydrogen bond; residue has a left-handed α configuration and is often Gly. The beginnings and ends of helices are also the sites of specific side-chain hydrogen-bonding patterns, referred to as N-caps and C-caps (Presta & Rose, 1988; Richardson & Richardson, 1988); these are described below.

β-sheets consist of short strands of polypeptide (typically 5–7 residues) running parallel or antiparallel and cross-linked by N—H···O=C hydrogen bonds. Although the (φ, ψ) angles of residues within β-sheets can be quite variable, the hydrogen-bonding patterns within these segments tend to be quite regular, as in the original Pauling models (Pauling & Corey, 1951). Occasional β-bulges in the middle of β-strands can interrupt the hydrogen-bonding pattern (Richardson et al., 1978), but otherwise disruptions occur only at the ends of strands. The hydrogen bonds in β-sheets appear to be slightly shorter than those in helices, by ∼0.1 Å, and also more linear (N—H···O ∼ 160°, compared with ∼157° in helices) (Baker & Hubbard, 1984). There also appears to be no difference between parallel and antiparallel β-sheets in the hydrogen-bond lengths and angles.

By far the most common type of turn is the β-turn, a sequence of four residues that brings about a reversal in the polypeptide chain direction. Hydrogen bonding does not seem to be essential for turn formation, but a common feature is a hydrogen bond between the C=O group of residue 1 and the NH group of residue 4, a 3₁₀-type, interaction. Turns are also often associated with characteristic side-chain–main-chain hydrogen-bond configurations (see below). The hydrogen bonds in turns tend to be longer and less linear than those in helices and β-sheets; in particular, the angle at the acceptor oxygen atom C—O···H is around 120° (Baker & Hubbard, 1984).

In addition to β-turns, a small but significant number of γ-turns are found. In these three-residue turns, a hydrogen bond is formed between the C=O of residue 1 and the NH of residue 3, an interaction. Although the approach to the acceptor oxygen atom is highly nonlinear (C—O···H ∼ 100°), the nonlinearity at the H atom is less pronounced (N—H···O ∼ 130–150°) (Baker & Hubbard, 1984). γ-turns are again of several types, depending on the configuration of the central residue. The classic γ-turn, first recognised by Matthews (1972) and Nemethy & Printz (1972), has a central residue with (φ, ψ) angles around (70°, −60°), which puts it in the normally disallowed region of the Ramachandran plot. More common, however, are structures in which an hydrogen bond is associated with a central residue with a configuration around (90°, −70°) (Baker & Hubbard, 1984); these structures are not necessarily true turns in the sense of bringing about a sharp chain reversal, however.

For hydrogen bonds involving sp² donors and/or acceptors, optimal interaction is expected to occur when the donor D—H group and the acceptor lone-pair orbital are coplanar (Taylor et al., 1983). Analysis of `in-plane' and `out-of-plane' components of N—H···O hydrogen bonds in proteins shows that these have characteristic values for different secondary structures (Artymiuk & Blake, 1981; Baker & Hubbard, 1984). The out-of-plane component is tightly clustered at ∼25° for helices and ∼60° for the most common β-turns (type I and type III), but is widely scattered around a mean of 0° for β-sheets. The latter reflects different twists or curvature of β-sheets. The large out-of-plane component for turns is consistent with a relatively weak interaction.