This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.104.044537v1 88/1/25    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vaccaro, L. Articles by Fraternali, F. Search for Related Content PubMed PubMed Citation Articles by Vaccaro, L. Articles by Fraternali, F.

Plasticity of Influenza Haemagglutinin Fusion Peptides and Their Interaction with Lipid Bilayers

Loredana Vaccaro ^*, Karen J. Cross ^*, Jens Kleinjung , Suzana K. Straus , David J. Thomas , Stephen A. Wharton ^*, John J. Skehel ^* and Franca Fraternali ^*

^* National Institute for Medical Research, London, United Kingdom; Bioinformatics Unit, Faculty of Sciences, Free University of Amsterdam, Amsterdam, The Netherlands; Department of Chemistry, University of British Columbia, Vancouver, British Columbia, Canada; and Biological Nuclear Magnetic Resonance Unit, Institute for Clinical Research, Medical School, University of Birmingham, Birmingham, United Kingdom

Correspondence: Address reprint requests to Franca Fraternali, Mill Hill, London NW7 1AA, London, UK. Tel.: 44-2088162250; Fax: 44-208906477; E-mail: ffranca{at}nimr.mrc.ac.uk.

A detailed molecular dynamics study of the haemagglutinin fusion peptide (N-terminal 20 residues of the HA2 subunits) in a model bilayer has yielded useful information about the molecular interactions leading to insertion into the lipids. Simulations were performed on the native sequence, as well as a number of mutant sequences, which are either fusogenic or nonfusogenic. For the native sequence and fusogenic mutants, the N-terminal 11 residues of the fusion peptides are helical and insert with a tilt angle of 30° with respect to the membrane normal, in very good agreement with experimental data. The tilted insertion of the native sequence peptide leads to membrane bilayer thinning and the calculated order parameters show larger disorder of the alkyl chains. These results indicate that the lipid packing is perturbed by the fusion peptide and could be used to explain membrane fusion. For the nonfusogenic sequences investigated, it was found that most of them equilibrate parallel to the interface plane and do not adopt a tilted conformation. The presence of a charged residue at the beginning of the sequence (G1E mutant) resulted in a more difficult case, and the outcomes do not fall straightforwardly into the general picture. Sequence searches have revealed similarities of the fusion peptide of influenza haemagglutinin with peptide sequences such as segments of porin, amyloid ß peptide, and a peptide from the prion sequence. These results confirm that the sequence can adopt different folds in different environments. The plasticity and the conformational dependence on the local environment could be used to better understand the function of fusion peptides.

This article has been cited by other articles:

				M. Sammalkorpi and T. Lazaridis Modeling a Spin-Labeled Fusion Peptide in a Membrane: Implications for the Interpretation of EPR Experiments Biophys. J., January 1, 2007; 92(1): 10 - 22. [Abstract] [Full Text] [PDF]

				Md. E. Haque, V. Koppaka, P. H. Axelsen, and B. R. Lentz Properties and Structures of the Influenza and HIV Fusion Peptides on Lipid Membranes: Implications for a Role in Fusion Biophys. J., November 1, 2005; 89(5): 3183 - 3194. [Abstract] [Full Text] [PDF]