Interaction of short modified peptides deriving from glycoprotein gp36 of feline immunodeficiency virus with phospholipid membranes.
A tryptophan-rich octapeptide, C8 (Ac-Trp-Glu-Asp-Trp-Val-Gly-Trp-Ile-NH(2)), modelled on the membrane-proximal external region of the feline immunodeficiency virus (FIV) gp36 glycoprotein ectodomain, exhibits potent antiviral activity against FIV. A mechanism has been proposed by which the peptide, being positioned on the surface of the cell membrane, inhibits its fusion with the virus. In the present work, peptide-lipid interactions of C8 with dimyristoyl phosphatidylcholine liposomes are investigated using electron spin resonance spectroscopy of spin-labelled lipids. Three other peptides, obtained from modifications of C8, have also been investigated, in an attempt to clarify the essential molecular features of the interactions involving the tryptophan residues. The results show that C8 adsorbs strongly on the bilayer surface. Membrane binding requires not only the presence of the Trp residues in the sequence, but also their common orientation on one side of the peptide that is engendered by the WX(2) WX(2) W motif. Membrane interaction correlates closely with peptide antiviral activity, indicating that the membrane is essential in stabilizing the peptide conformation that will be able to inhibit viral infection.
D'Errico
Gerardino
G
Dipartimento di Chimica Paolo Corradini, Università di Napoli Federico II, Complesso di Monte S. Angelo, Via Cinthia, 80126, Naples, Italy. gerardino.derrico@unina.it
Vitiello
Giuseppe
G
D'Ursi
Anna Maria
AM
Marsh
Derek
D
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002942:Circular Dichroism; D004578:Electron Spin Resonance Spectroscopy; D006023:Glycoproteins / Q000737:chemistry*; D016089:Immunodeficiency Virus, Feline / Q000502:physiology; D008051:Lipid Bilayers / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D017186:Titrimetry; D014364:Tryptophan; D014764:Viral Proteins / Q000737:chemistry*; D053586:Virus Internalization
D000998:Antiviral Agents; D006023:Glycoproteins; D008051:Lipid Bilayers; D009842:Oligopeptides; D010743:Phospholipids; D014764:Viral Proteins; D014364:Tryptophan