Computational study of lipid-destabilizing protein fragments: Towards a comprehensive view of tilted peptides

Citation
L. Lins et al., Computational study of lipid-destabilizing protein fragments: Towards a comprehensive view of tilted peptides, PROTEINS, 44(4), 2001, pp. 435-447
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEINS-STRUCTURE FUNCTION AND GENETICS
ISSN journal
0887-3585 → ACNP
Volume
44
Issue
4
Year of publication
2001
Pages
435 - 447
Database
ISI
SICI code
0887-3585(20010901)44:4<435:CSOLPF>2.0.ZU;2-D
Abstract
Tilted peptides are short sequence fragments (10-20 residues long) that pos sess an asymmetric hydrophobicity gradient along their sequence when they a re helical. Due to this gradient, they adopt a tilted orientation towards a single lipid/water interface and destabilize the lipids. We have detected those peptides in many different proteins with various functions. While bei ng all tilted-oriented at a single lipid/water interface, no consensus sequ ence can be evidenced. In order to better understand the relationships betw een their lipid-destabilizing activity and their properties, we used IMPALA to classify the tilted peptides. This method allows the study of interacti ons between a peptide and a modeled lipid bilayer using simple restraint fu nctions designed to mimic some of the membrane properties. We predict that tilted peptides have access to a wide conformational space in membranes, in contrast to transmembrane and amphipathic helices. In agreement with previ ous studies, we suggest that those metastable configurations could lead to the perturbation of the acyl chains organization and could be a general mec hanism for lipid destabilization. Our results further suggest that tilted p eptides fall into two classes: those from proteins acting on membrane behav e differently than destabilizing fragments from interfacial proteins. While the former have equal access to the two layers of the membrane, the latter are confined within a single lipid layer. This could be in relation with t he organization of lipid substrate on which the peptides physiologically ac t. Proteins 2001;44:435-447. (C) 2001 Wiley-Liss, Inc.