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PMID: 15809312 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

Class II fusion protein of alphaviruses drives membrane fusion through the same pathway as class I proteins.

The Journal of cell biology ·Vol. 169 ·No. 1 ·2005-04-11 ·Pages 167-77

Zaitseva E, Mittal A, Griffin DE, Chernomordik LV

Abstract

Viral fusion proteins of classes I and II differ radically in their initial structures but refold toward similar conformations upon activation. Do fusion pathways mediated by alphavirus E1 and influenza virus hemagglutinin (HA) that exemplify classes II and I differ to reflect the difference in their initial conformations, or concur to reflect the similarity in the final conformations? Here, we dissected the pathway of low pH-triggered E1-mediated cell-cell fusion by reducing the numbers of activated E1 proteins and by blocking different fusion stages with specific inhibitors. The discovered progression from transient hemifusion to small, and then expanding, fusion pores upon an increase in the number of activated fusion proteins parallels that established for HA-mediated fusion. We conclude that proteins as different as E1 and HA drive fusion through strikingly similar membrane intermediates, with the most energy-intensive stages following rather than preceding hemifusion. We propose that fusion reactions catalyzed by all proteins of both classes follow a similar pathway.

MeSH Terms
Alphavirus/metabolism Cells, Cultured Erythrocytes/physiology,virology Hemagglutinin Glycoproteins, Influenza Virus/metabolism Humans Lipids/chemistry Membrane Fusion/physiology Protein Binding Protein Folding Viral Fusion Proteins/metabolism
Chemicals
Hemagglutinin Glycoproteins, Influenza Virus Lipids Viral Fusion Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Zaitseva Elena
Section on Membrane Biology, Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Mittal Aditya
Griffin Diane E
Chernomordik Leonid V
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200412059
Published
2005-04-11
Epub
2005-00-04
Pages
167-77
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2171914
Subset
IM
Grants
NINDS NIH HHS · R01 NS018596 · United States
NINDS NIH HHS · R01 NS038932 · United States
NINDS NIH HHS · NS18596 · United States
External Links
PubMed source DOI: 10.1083/jcb.200412059 PMC Full Text View journal details
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