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

Abstract

The work presents the results of an exhaustive conformational analysis of β-turns involving amino acid residues with disallowed backbone conformation of the polypeptide chain. It is known that the first residue of the β-turn (Asn47) of the distal β-hairpin in the α-spectrin SH3-domain is characterized by sterically disallowed main chain conformation (values of the dihedral angles (φ and ψ are in the right bottom quadrant of the Ramachandran plot). All α-spectrin structures with the anomalous elements deposited in the PDB were analysed. We hypothesized that the formation of disallowed conformation may occur through the fixation (due to the SH3 domain structure) of the adjacent to the β-turn amino acid residues with the β-structure. These residues are disposed in such a manner that β-turn conformation of the residues contributes just to the disallowed local conformation of this residue whereas any other β-turn conformations (with allowed local conformation) are impossible. To test this hypothesis an exhaustive conformational analysis of the β-bend has been performed by altering internal coordinates (two pairs of φ and ψ angles and two Ω angles). The conformations were selected as a result of grid search procedure with. 1 degrees step that corresponded to stereochemically allowed local deformations of the polypeptide chain segment forming the β-turn. In all conformations obtained the local conformation of Asn47 rests in the disallowed region. The conformations found include conformations coinciding with experimentally determined structures from the PDB as well as an additional variant that differs from X-ray structure in values of a pair of φ and ψ angles of the second residue belonging to the β-bend. Values of these angles fall in the region of the Ramachandran plot near the line φ = 0 (and negative values of ψ) i.e. in strongly disallowed region without experimental points. Therefore the additional variants of the β-turn local deformation are impossible to observe in experiment. Thus, the idea that disallowed conformation is intruded to the β-bend by fixation of adjacent residues receives confirmation in this work. The topological limitations in a context of the structure in such kind of β-hairpins exclude the allowed local conformations.