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PMID: 9508770 Published · ppublish English Journal Article

The pathway of membrane fusion catalyzed by influenza hemagglutinin: restriction of lipids, hemifusion, and lipidic fusion pore formation.

The Journal of cell biology ·Vol. 140 ·No. 6 ·1998-03-23 ·Pages 1369-82

Chernomordik LV, Frolov VA, Leikina E, Bronk P, Zimmerberg J

Abstract

The mechanism of bilayer unification in biological fusion is unclear. We reversibly arrested hemagglutinin (HA)-mediated cell-cell fusion right before fusion pore opening. A low-pH conformation of HA was required to form this intermediate and to ensure fusion beyond it. We present evidence indicating that outer monolayers of the fusing membranes were merged and continuous in this intermediate, but HA restricted lipid mixing. Depending on the surface density of HA and the membrane lipid composition, this restricted hemifusion intermediate either transformed into a fusion pore or expanded into an unrestricted hemifusion, without pores but with unrestricted lipid mixing. Our results suggest that restriction of lipid flux by a ring of activated HA is necessary for successful fusion, during which a lipidic fusion pore develops in a local and transient hemifusion diaphragm.

MeSH Terms
Cells, Cultured Cold Temperature Coloring Agents/pharmacokinetics Hemagglutinin Glycoproteins, Influenza Virus/chemistry,pharmacology Humans Hydrogen-Ion Concentration Lipid Bilayers/metabolism Lipid Metabolism Membrane Fusion/drug effects,physiology Protein Conformation
Chemicals
Coloring Agents Hemagglutinin Glycoproteins, Influenza Virus Lipid Bilayers
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chernomordik L V
Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1855, USA. lchern@helix.nih.gov
Frolov V A
Leikina E
Bronk P
Zimmerberg J
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.140.6.1369
Email
lchern@helix.nih.gov
Published
1998-03-23
Pages
1369-82
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2132678
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.140.6.1369 PMC Full Text View journal details
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