Analysis of short loops connecting secondary structural elements in proteins

Abstract

The recognition by Ramachandran et al. (1) that the range of polypeptide chain conformation is limited by steric constraints constitutes the first step in defining the limits of the problem of protein folding. The srystal structures of globular proteins reveal intricate arrays of secondary structure modules, separated by irregular elements of the polypeptide chain termed as loops, which are uniquely assembled to yield the native folded conformation (2,3). While much early work in the area of protein structure analysis focused on the regular elements of the structure, it is becoming increasingly apparent that the less regular segments or loops merit detailed study (4-10). Protein engineering appeoaches which permit transfer of loops from one context to another or allow truncation of connecting elements (11-13), have provided a fresh impetus to the present study, short loops (≤5 residues) connecting secondary structure modules are identitied from a data set of 65, largely non-homologous, protein crystal structures. Four types of super-secondary structural motifs involving α-helices and b-strands viz. αα, ββ, αβ and βα are considered and the conformational and composotional properties of the connecting loops are examined. An analysis of the spatial orientation of the two linked secondary structural elements reveals reasonably frequent occurrence of an 'L'-shaped motif involving two orthogonally disposed B-strands.