Viral fusion glycoproteins present a membrane-proximal external region (MPER) which is usually rich in aromatic residues and exhibits a marked tendency to stably reside at the membrane interfaces, leading, through unknown mechanisms, to a destabilization of the bilayer structure. This step has been proposed to be fundamental for the fusion process between target membrane and viral envelope. In the present work, we investigate the interaction between an octapeptide (C8) deriving from the MPER domain of gp36 of feline immunodeficiency virus and POPC bilayers by combining experimental results obtained by neutron reflectivity, electron spin resonance, circular dichroism, and fluorescence spectroscopy with molecular dynamics simulations. Our data indicate that C8 binds to the lipid bilayer adsorbing onto the membrane surface without deep penetration. As a consequence of this interaction, the bilayer thickness decreases. The association of the peptide with the lipid membrane is driven by hydrogen bonds as well as hydrophobic interactions that the Trp side chains form with the lipid headgroups. Upon peptide-bilayer interaction, C8 forms transient secondary structures ranging from 3(10) helices to turn conformations, while acyl chains of the peptide-exposed POPC molecules assume a more ordered packing. At the same time, lipid headgroups' hydration increases. The asymmetric lipid bilayer perturbation is proposed to play a fundamental role in favoring the membrane fusion process.
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|Titolo:||Destabilization of lipid membranes by a Peptide derived from Glycoprotein gp36 of feline immunodeficiency virus: a combined molecular dynamics/experimental study|
|Rivista:||JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL|
|Citazione:||Merlino, A., Vitiello, G., Grimaldi, M., Sica, F., Busi, E., Basosi, R., et al. (2012). Destabilization of lipid membranes by a Peptide derived from Glycoprotein gp36 of feline immunodeficiency virus: a combined molecular dynamics/experimental study. JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL, 116(1), 401-412.|
|Appare nelle tipologie:||1.1 Articolo in rivista|