The interactions of the N-terminal fusogenic peptide of HIV-1 gp41 with neutral phospholipids |
| |
Authors: | C Curtain Frances Separovic Katherine Nielsen David Craik Yong Zhong Alan Kirkpatrick |
| |
Institution: | (1) Department of Physics, Monash University, Clayton, Victoria 3168, Australia e-mail: ccurtain@vaxc.cc.monash.edu.au, AU;(2) School of Chemistry, University of Melbourne, Parkville, Victoria 3052, Australia, AU;(3) Centre for Drug Design and Development, Gerhmann Laboratories, University of Queensland, Queensland 4072, Australia, AU;(4) CSIRO Division of Molecular Science, Parkville, Victoria 3052, Australia, AU |
| |
Abstract: | We have studied the interactions with neutral phospholipid bilayers of FPI, the 23-residue fusogenic N-terminal peptide of
the HIV-1LAI transmembrane glycoprotein gp41, by CD, EPR, NMR, and solid state NMR (SSNMR) with the objective of understanding how it
lyses and fuses cells. Using small unilamellar vesicles made from egg yolk phoshatidylcholine which were not fused or permeabilised
by the peptide we obtained results suggesting that it was capable of inserting as an α-helix into neutral phospholipid bilayers but was only completely monomeric at peptide/lipid (P/L) ratios of 1/2000 or lower.
Above this value, mixed populations of monomeric and multimeric forms were found with the proportion of multimer increasing
proportionally to P/L, as calculated from studies on the interaction between the peptide and spin-labelled phospholipid. The
CD data indicated that, at P/L between 1/200 and 1/100, approximately 68% of the peptide appeared to be in α-helical form. When P/L=1/25 the α-helical content had decreased to 41%. Measurement at a P/L of 1/100 of the spin lattice relaxation effect on the 13C nuclei of the phospholipid acyl chains of an N-terminal spin label attached to the peptide showed that most of the peptide
N-termini were located in the interior hydrocarbon region of the membrane. SSNMR on multilayers of ditetradecylphosphatidyl
choline at P/Ls of 1/10, 1/20 and 1/30 showed that the peptide formed multimers that affected the motion of the lipid chains
and disrupted the lipid alignment. We suggest that these aggregates may be relevant to the membrane-fusing and lytic activities
of FPI and that they are worthy of further study.
Received: 8 June 1998 / Revised version: 18 November 1998 / Accepted: 28 December 1998 |
| |
Keywords: | HIV-1 fusion peptide EPR NMR Solid state NMR Circular dichroism |
本文献已被 SpringerLink 等数据库收录! |
|