Principles of Protein Structural Organization - G. Schultz 1982

Mechanisms of Polypeptide Chain Folding and Association
Secondary Structure
Reverse Turns of the Peptide Chain

The peptide chain can form sharp turns that involve hydrogen bonding. When investigating the preferred Conformations of three consecutively positioned peptide units (from Cⁱ_a to Cⁱ⁺³_a), Venkatachalam [199] discovered three structures stabilized by Hydrogen Bonds between the O_i and N_i+3 atoms. These were designated as reverse chain turns I, II, and III. Turn III represents a segment of the aforementioned 3₁₀-helix (Fig. 5.4). Turn I is a distorted 3₁₀-helix in which the dihedral angles (∅, ψ) of the regular helix take on slightly different values for Cⁱ⁺¹_a and Cⁱ⁺²_a (Fig. 5.7, a). In turn II, the plane of the peptide group between the residues at positions i + 1 and i + 2 undergoes a sharp change in orientation (Fig. 5.7, b), and the (∅, ψ) angles at the Cⁱ⁺²_a atoms acquire substantially different values (Fig. 5.7, a). This leads to severe steric clashes between the O_i+1 atom and the side chain of the i+2 residue; however, no strain arises in the chain for turn II if a Gly residue is present at position i+2. The mirror images of reverse turns I, II, and III, referred to as turns I', II', and III', are sterically unfavorable.

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Fig. 5.6. Reverse chain turns.

a — Regions of the backbone dihedral angles for the i+1 residue (dashed line) and i+2 residue (solid line) in type I, II, and III reverse turns [199]. The corresponding regions are connected by arrows. In the case of turn III, both regions coincide with each other and with THE POSITION OF the 3₁₀-helix (Fig. 5.4). b — turns of types I and II [326]. Type II exhibits steric hindrance between the R_i+2 side chain and O_i+1, requiring a Gly residue at position i+2. For a type III turn, see Fig. 5.4.

Reverse chain turns frequently occur in Proteins. Analysis of chain turns in Globular proteins has shown that they are very common, with about one-quarter of all residues participating in their formation [200, 201]. Furthermore, turns I, II, and III were found to account for 35, 15, and 15% of their total number, respectively [202]. As expected, almost all identified type II turns contain a Gly residue at position i+2. The overall prevalence of mirror-image turns (turns I', II', and III') is low, as anticipated, at 10%. Non-standard reverse turns lacking hydrogen bonds occur with a frequency of 25%. They are identified using a more general criterion, according to which the distance between the Cⁱ_a and Cⁱ⁺³_a atoms must be less than 7 Å while the backbone adopts a conformation other than an a-helix. This criterion encompasses all standard chain turns while also allowing for the possibility of other reverse conformations. Occasionally, non-standard turns contain cis-Pro; notably Pro-93 and Pro-114 in Ribonuclease [39], Pro-168 in subtilisin [40], and Pro-116 in staphylococcal nuclease [41].

The majority of turns are located on the protein surface. Analyzing the spatial distribution of turns in proteins, Kuntz [203] found that they are concentrated On the surface. Consistent with this Location, they predominantly consist of hydrophilic residues. It is hypothesized that turns play merely a passive role during the folding process, forming regions of least resistance to non-covalent forces that tend to bend the chain. This hypothesis is supported by the wide variety of observed turns, none of which exhibits a particularly stable conformation.