Disallowed conformations of a polypeptide chain as exemplified by the β-turn of the β-hairpin in the α-spectrin SH3 domain

• Published in: Biophysics (Oxford) Vol. 60; no. 1; pp. 1 - 9
• Main Authors: Uroshlev, L. A., Torshin, I. Yu, Batyanovskii, A. V., Esipova, N. G., Tumanyan, V. G.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 2015
• Subjects: Biological and Medical Physics; Biophysics; Molecular Biophysics; Physics; Physics and Astronomy; SH3 domain; β-turn; conformational analysis; disallowed conformations
• ISSN: 0006-3509; 1555-6654
• DOI: 10.1134/S0006350915010236

A comprehensive conformational analysis has been performed of β-turns containing an amino acid with a disallowed conformation of the polypeptide chain backbone. The first residue of the β-turn (Asn47) of the distal β-hairpin in the α-spectrin SH3 domain is characterized by a sterically disallowed back-bone conformation, with values of dihedral angles Φ and ψ being in the right bottom quadrant of the Ramachandran plot). Based on analysis of all α-spectrin structures with an anomalous element deposited in the PDB, the hypothesis has been proposed that the disallowed conformation may result from the fixation (conditioned by the SH3 domain structure) of β-structure residues adjacent to the β-turn, which are arranged so that such a residue can adopt only a disallowed conformation, excluding the possibility of other β-turn conformations (with an allowed local conformation). To test this hypothesis, a conformational analysis of the β-turn was performed by varying all its internal coordinates (two pairs of Φ and ψ angles and two ω angles). As a result of a grid search procedure with a 1° step, variants were selected that corresponded to stereochemically allowed local deformations in the polypeptide chain segment forming the β-turn. However, the local conformation of the Asn47 residue in all these variants proved to remain in the disallowed region. These variants included conformations coinciding with experimentally determined strictures from the PDB as well as an additional variant differing from them in the pair of Φ and ψ angles at the second residue of the β-turn: in the Ramachandran plot, they fall into the region near the line Φ = 0 and negative ψ values, i.e., into the strongly disallowed region where no experimental points have been recorded. Thus, the results of this study confirm the hypothesis that the disallowed conformation is “imposed” on the β-turn due to fixation of residues adjacent to it. Topological structural limitations in β-hairpins of such a type exclude the possibility of allowed local conformations.