HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 25, 18388-18396, June 22, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/25/18388    most recent M700099200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Google Scholar Google Scholar Articles by Lorin, A. Articles by Brasseur, R. Search for Related Content PubMed PubMed Citation Articles by Lorin, A. Articles by Brasseur, R. Social Bookmarking                      What's this?

Mode of Membrane Interaction and Fusogenic Properties of a de Novo Transmembrane Model Peptide Depend on the Length of the Hydrophobic Core^*

Aurélien Lorin¹², Benoit Charloteaux¹, Yael Fridmann-Sirkis, Annick Thomas³, Yechiel Shai⁴, and Robert Brasseur⁵

From the Gembloux Agricultural University, Centre de Biophysique Moléculaire Numérique, B-5030 Gembloux, Belgium and the Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel

Model peptides composed of alanine and leucine residues are often used to mimic single helical transmembrane domains. Many studies have been carried out to determine how they interact with membranes. However, few studies have investigated their lipid-destabilizing effect. We designed three peptides designated KALRs containing a hydrophobic stretch of 14, 18, or 22 alanines/leucines surrounded by charged amino acids. Molecular modeling simulations in an implicit membrane model as well as attenuated total reflection-Fourier transform infrared analyses show that KALR is a good model of a transmembrane helix. However, tryptophan fluorescence and attenuated total reflection-Fourier transform infrared spectroscopy indicate that the extent of binding and insertion into lipids increases with the length of the peptide hydrophobic core. Although binding can be directly correlated to peptide hydrophobicity, we show that insertion of peptides into a membrane is determined by the length of the peptide hydrophobic core. Functional studies were performed by measuring the ability of peptides to induce lipid mixing and leakage of liposomes. The data reveal that whereas KALR₁₄ does not destabilize liposomal membranes, KALR₁₈ and KALR₂₂ induce 40 and 50% of lipid-mixing, and 65 and 80% of leakage, respectively. These results indicate that a transmembrane model peptide can induce liposome fusion in vitro if it is long enough. The reasons for the link between length and fusogenicity are discussed in relation to studies of transmembrane domains of viral fusion proteins. We propose that fusogenicity depends not only on peptide insertion but also on the ability of peptides to destabilize the two leaflets of the liposome membrane.

Received for publication, January 4, 2007 , and in revised form, April 24, 2007.

^* This work was supported by MinistèredelaRégion Wallonne Contract 14540 (PROTMEM) and Contract 215140 (BUSTEC). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ These authors contributed equally to this work.

² Supported by National Fund for Scientific Research of Belgium Grant F.N.R.S.-Televie 7.4.527.05 [EC] .F.

³ Research Director at INSERM (France).

⁴ Holder of the Harold S. and Harriet B. Brady Professorial Chair in Cancer Research. Supported by the Israel Science Foundation.

⁵ Research Director of the National Funds for Scientific Research of Belgium. To whom correspondence should be addressed. Tel.: 32-81-62-25-21; Fax: 32-81-62-25-22; E-mail: brasseur.r{at}fsagx.ac.be.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?