Departmental Papers (BE)

Document Type

Journal Article

Date of this Version

January 2004

Comments

Reprinted from Biophysical Journal, Volume 86, Issue 1, January 2004, pages 272-284.
Publisher URL: http://www.biophysj.org/cgi/reprint/86/1/272

Abstract

A key element of membrane fusion reactions in biology is the involvement of specific fusion proteins. In many viruses, the proteins that mediate membrane fusion usually exist as homotrimers. Furthermore, they contain extended triplehelical coiled-coil domains and fusogenic peptides. It has been suggested that the coiled-coil domains present the fusogenic peptide in a conformation or geometry favorable for membrane fusion. To test the hypothesis that trimerization of fusogenic peptide is related to optimal fusion, we have designed and synthesized a triple-stranded coiled-coil X31 peptide, also known as the ccX31, which mimics the influenza virus hemagglutinin fusion peptide in the fusion-active state. We compared the membrane interactive properties of ccX31 versus the monomeric X31 fusogenic peptide. Our data show that trimerization enhances peptide-induced leakage of liposomal contents and lipid mixing. Furthermore, studies using micropipette aspiration of single vesicles reveal that ccX31 decreases lysis tension, τlysis, but not area expansion modulus, Ka, of phospholipid bilayers, whereas monomeric X31 peptide lowers both τlysis and Ka. Our results are consistent with the hypothesis that oligomerization of fusogenic peptide promotes membrane fusion, possibly by enhancing localized destabilization of lipid bilayers.

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Date Posted: 21 January 2005

This document has been peer reviewed.