Logo image
Membrane Fusion Mediated by Coiled Coils: A Hypothesis
Journal article   Open access   Peer reviewed

Membrane Fusion Mediated by Coiled Coils: A Hypothesis

Joe Bentz
Biophysical journal, v 78(2), pp 886-900
2000
PMID: 10653801
url
https://doi.org/10.1016/s0006-3495(00)76646-xView
Published, Version of Record (VoR)Open Access (Publisher-Specific) Open
url
https://doi.org/10.1016/S0006-3495(00)76646-XView
Published, Version of Record (VoR) Open

Abstract

DOPE HIV TBHA2 HA BHA Env GD1a DOPC LPC SNARE
A molecular model of the low-pH-induced membrane fusion by influenza hemagglutinin (HA) is proposed based upon the hypothesis that the conformational change to the extended coiled coil creates a high-energy hydrophobic membrane defect in the viral envelope or HA expressing cell. It is known that 1) an aggregate of at least eight HAs is required at the fusion site, yet only two or three of these HAs need to undergo the “essential” conformational change for the first fusion pore to form (Bentz, J. 2000. Biophys. J. 78:000–000); 2) the formation of the first fusion pore signifies a stage of restricted lipid flow into the nascent fusion site; and 3) some HAs can partially insert their fusion peptides into their own viral envelopes at low pH. This suggests that the committed step for HA-mediated fusion begins with a tightly packed aggregate of HAs whose fusion peptides are inserted into their own viral envelope, which causes restricted lateral lipid flow within the HA aggregate. The transition of two or three HAs in the center of the aggregate to the extended coiled coil extracts the fusion peptide and creates a hydrophobic defect in the outer monolayer of the virion, which is stabilized by the closely packed HAs. These HAs are inhibited from diffusing away from the site to admit lateral lipid flow, in part because that would initially increase the surface area of hydrophobic exposure. The other obvious pathway to heal this hydrophobic defect, or some descendent, is recruitment of lipids from the outer monolayer of the apposed target membrane, i.e., fusion. Other viral fusion proteins and the SNARE fusion protein complex appear to fit within this hypothesis.

Metrics

11 Record Views
122 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Biophysics
Logo image