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Registering α-helices and β-strands using backbone C[BOND]H…O interactions



The possible occurrence of a novel helix terminating structural motif in proteins involving a stabilizing short C[BOND]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[BOND]H…O hydrogen bond between the T-4 CαH and the T+1 C[DOUBLE BOND]O groups, where T is the helix terminator adopting a left handed (αL) 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[BOND]H…O interactions with a regular periodicity. Model building resulted in the generation of idealized αβ and βα motifs, which can then be generalized to higher-order repetitive structures. Inspection of the antiparallel αβ motif revealed a significant propensity for Ser, Glu, and Gln residues at the T-4 position resulting in further stabilization using an O…H[BOND]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. Proteins 2003;51:167–171. © 2003 Wiley-Liss, Inc.