Beta-Hairpins in proteins revisited: lessons for de novo design

Gunasekaran, K and Ramakrishnan, C and Balaram, P (1997) Beta-Hairpins in proteins revisited: lessons for de novo design. In: Protein Engineering, 10 (10). pp. 1131-1141.

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Abstract

Beta-Hairpins with short connecting loops (1-5 residues) have been identified from a data set of 250 non-homologous, high resolution (< or =2.0 A) protein crystal structures. The conformational preferences of the loop segments have been analyzed with the specific aim of identifying frequently occurring motifs. Type I' and II' beta-turns were found to have a high propensity for occurrence in two residue loops. For three and four residue loops, the major conformational motif in the linking segments is alphaR-alphaR-alphaL (type I beta-turn followed by a residue in a left-handed helical conformation) and alphaR- alphaR-alphaR-alphaL (a pi-turn motif), respectively. The present larger data set confirms the high occurrences of these motifs which have been identified in earlier analyses. In addition to type I' and type II' beta-turns, several examples of type I beta-turn nucleated two residue loop hairpins, in spite of having an opposing sense of twist to that of type I' beta-turn, have also been observed. Examination of these frequently occurring motifs (flanked by extended conformation [beta]) in the data set reveals that the motifs beta-alphaR-alphaR- alphaL-beta and beta-type I'-beta have equal propensity and type II' indeed having highest propensity to nucleate beta-hairpins. The larger number of examples in this study allows the estimation of the specific amino acid preferences for loop positions in two, three and four residue loops. Small polar residues Asn, Asp, Ser, Thr, Gly and Pro in general have a high propensity for the loop positions but they reveal specific positional preferences in these frequently occurring motifs. There are no strong compositional preferences in the strand segments. Amino acid pair correlations across strands also do not show any significant pattern, with the exception of Cys-Cys pairs. Several Cys- Cys pairs have been identified at the non-hydrogen bonded positions of beta-hairpins; as many as six are disulfide bonded pairs. An examination of longer loop length hairpins reveals that the distortions of hairpins nucleated by tight turns (two residues) are much less frequently observed. The results presented in this study provide inputs for the de novo design of consensus loop segments in synthetic hairpins.

Item Type:	Journal Article
Publication:	Protein Engineering
Publisher:	Oxford University Press
Additional Information:	Copyright for this article belongs to Oxford University Press. The journal is currently known as Protein Engineering, Design and Publication.
Keywords:	beta-hairpins;hairpin design;protein data analysis;short loop motifs;turns in proteins
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	26 Oct 2004
Last Modified:	19 Sep 2010 04:16
URI:	http://eprints.iisc.ac.in/id/eprint/2194

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