ß-Bulges: extensive structural analyses of ß-sheets irregularities.

ABSTRACT

ß-Sheets are quite frequent in protein structures and are stabilized by regular main-chain hydrogen bond patterns. Irregularities in ß-sheets, named ß-bulges, are distorted regions between two consecutive hydrogen bonds. They disrupt the classical alternation of side chain direction and can alter the directionality of ß-strands. They are implicated in protein-protein interactions and are introduced to avoid ß-strand aggregation. Five different types of ß-bulges are defined. Previous studies on ß-bulges were performed on a limited number of protein structures or one specific family. These studies evoked a potential conservation during evolution. In this work, we analyze the ß-bulge distribution and conservation in terms of local backbone conformations and amino acid composition. Our dataset consists of 66 times more ß-bulges than the last systematic study (Chan et al. Protein Science 1993, 21574-1590). Novel amino acid preferences are underlined and local structure conformations are highlighted by the use of a structural alphabet. We observed that ß-bulges are preferably localized at the N- and C-termini of ß-strands, but contrary to the earlier studies, no significant conservation of ß-bulges was observed among structural homologues. Displacement of ß-bulges along the sequence was also investigated by Molecular Dynamics simulations.