β-Breakers: An aperiodic secondary structure

Abstract We have studied the architecture of parallel β-sheets in proteins and focused on the residues that initiate and terminate the β-strands. These β-breaker residues are at the origin of the kink between the β-strand and the turn that precedes or follows it. β-Breakers can be located automatically using a consensus approach based on algorithmic secondary structure assignment, solvent accessibility and backbone dihedral angles. These β-breakers are conformationally homogeneous with respect to side-chain solvent accessibility and backbone dihedral angle profile. A sequence-structure correlation is noted: a restricted subset of amino acids is observed at these positions. Analysis of homologous protein sequences shows that these residues are more highly conserved than other residues in the loop. We conclude that β-breakers are the structural analogs of the N and C-terminal caps of α-helices. The identification of this aperiodic substructure suggests a strategy for improving secondary structure prediction and may guide site-directed mutagenesis experiments.