Interaction of a peptide derived from glycoprotein gp36 of feline immunodeficiency virus and its lipoylated analogue with phospholipid membranes.
P59, a 20-mer peptide modeled on the membrane-proximal external region (MPER) of the feline immunodeficiency virus (FIV) gp36 ectodomain, has potent antiviral activity. The lipoylated analogue, lipo-P59, displays a similar activity, which is preferentially retained by cellular substrates. A mechanism has been proposed recently in which the peptide, being positioned on the surface of the cell membrane, inhibits its fusion with the virus; the lipophilic chain of lipo-P59 is thought to insert into the membrane interior, thus anchoring the peptide at the surface. In the present work, lipid-peptide interactions of P59 and lipo-P59 with phospholipid liposomes are investigated using spin-label electron spin resonance spectroscopy. Two phospholipids have been examined, the zwitterionic dimyristoyl phosphatidylcholine and the anionic dimyristoyl phosphatidylglycerol, and a wide range of lipid spin labels, including positional isomers. Independent of the membrane charge, both peptides bind to lipid bilayers; however, whereas P59 insertion between the lipid headgroups leads to significant liposome destabilization, eventually resulting in vesicle fragmentation with the formation of smaller aggregates, lipo-P59 inserts with the lipophilic tail among the lipid chains, while the peptidic portion remains adsorbed onto the membrane, where it can effectively exert its antiviral activity.
D'Errico
Gerardino
G
Dipartimento di Chimica, Università di Napoli "Federico II", Napoli, Italy, Dipartimento di Scienze Farmaceutiche, Università di Salerno, Fisciano, Italy.
D'Ursi
Anna Maria
AM
Marsh
Derek
D
D004578:Electron Spin Resonance Spectroscopy; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D016089:Immunodeficiency Virus, Feline / Q000737:chemistry / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D054878:Lipoylation; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013696:Temperature; D017186:Titrimetry; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism*; D014867:Water / Q000737:chemistry
D006023:Glycoproteins; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010743:Phospholipids; D014764:Viral Proteins; D014867:Water