Registering α-helices and β-strands using backbone C-H...O interactions

Abstract

The possible occurrence of a novel helix terminating structural motif in proteins involving a stabilizing short C-H...O interaction has been examined using a dataset of 634 non-homologous protein structures (≤2.0 Å). The search for this motif was prompted by the crystallographic characterization of a novel structural feature in crystals of a synthetic decapeptide in which extension of a Schellman motif led to the formation of a C-H...O hydrogen bond between the T-4 C^αH and the T+1 C=O groups, where T is the helix terminator adopting a left handed (α_L) conformation. More than 100 such motifs with backbone conformation superposing well with the peptide examples were identified. In several examples, formation of this motif led to an approximately antiparallel arrangement of a helical segment with an extended β-strand. Careful examination of these examples suggested the possibility of registering antiparallel arrangement of helices and strands by means of backbone C-H...O interactions with a regular periodicity. Model building resulted in the generation of idealized and motifs, which can then be generalized to higher-order repetitive structures. Inspection of the antiparallel motif revealed a significant propensity for Ser, Glu, and Gln residues at the T-4 position resulting in further stabilization using an O...H-N side-chain-backbone hydrogen bond. Modeling studies revealed ready accommodation of serine residues along the helix face that contacts the strand. The theoretically generated folds correspond to "open" polypeptide structures.