| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
¶ 
¶
* Department of Biochemistry and Molecular Biophysics, School of Medicine; Departments of Chemical and Biomolecular Engineering and Bioengineering, School of Engineering and Applied Science; and ¶ Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania USA
Correspondence: Address reprint requests to William F. DeGrado, Dept. of Biochemistry and Molecular Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104. Tel.: 215-898-4590; Fax: 215-573-7229; E-mail: wdegrado{at}mail.med.upenn.edu; and Daniel A. Hammer, Dept. of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104. Tel.: 215-573-6761; Fax: 215-573-2071; E-mail: hammer{at}seas.upenn.edu.
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 triple-helical 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, 
lysis, but not area expansion modulus, Ka, of phospholipid bilayers, whereas monomeric X31 peptide lowers both lysis 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.
This article has been cited by other articles:
 |
|
 |
|
  S.-R. Wu, L. Haag, M. Sjoberg, H. Garoff, and L. Hammar The Dynamic Envelope of a Fusion Class II Virus: E3 DOMAIN OF GLYCOPROTEIN E2 PRECURSOR IN SEMLIKI FOREST VIRUS PROVIDES A UNIQUE CONTACT WITH THE FUSION PROTEIN E1 J. Biol. Chem., September 26, 2008; 283(39): 26452 - 26460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Ambroggio, F. Separovic, J. H. Bowie, G. D. Fidelio, and L. A. Bagatolli Direct Visualization of Membrane Leakage Induced by the Antibiotic Peptides: Maculatin, Citropin, and Aurein Biophys. J., September 1, 2005; 89(3): 1874 - 1881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Vaccaro, K. J. Cross, J. Kleinjung, S. K. Straus, D. J. Thomas, S. A. Wharton, J. J. Skehel, and F. Fraternali Plasticity of Influenza Haemagglutinin Fusion Peptides and Their Interaction with Lipid Bilayers Biophys. J., January 1, 2005; 88(1): 25 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Jin, C. Carlile, S. Nolan, and E. Grote Prm1 Prevents Contact-Dependent Lysis of Yeast Mating Pairs Eukaryot. Cell, December 1, 2004; 3(6): 1664 - 1673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Ritter, K. Boesze-Battaglia, B. M. Tam, O. L. Moritz, N. Khattree, S.-C. Chen, and A. F. X. Goldberg Uncoupling of Photoreceptor Peripherin/rds Fusogenic Activity from Biosynthesis, Subunit Assembly, and Targeting: A POTENTIAL MECHANISM FOR PATHOGENIC EFFECTS J. Biol. Chem., September 17, 2004; 279(38): 39958 - 39967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Huang, C.-L. Chen, and A. Herrmann Bilayer Conformation of Fusion Peptide of Influenza Virus Hemagglutinin: A Molecular Dynamics Simulation Study Biophys. J., July 1, 2004; 87(1): 14 - 22. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
