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PMID: 8917512 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Studies using double mutants of the conformational transitions in influenza hemagglutinin required for its membrane fusion activity.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 23 ·1996-11-12 ·Pages 12873-8

Steinhauer DA, Martín J, Lin YP, Wharton SA, Oldstone MB, Skehel JJ, Wiley DC

Abstract

Amino acid substitutions widely distributed throughout the influenza hemagglutinin (HA) influence the pH of its membrane fusion activity. We have combined a number of these substitutions in double mutants and determined the effects on the pH of fusion and on the pH at which the refolding of HA required for fusion occurs. By analyzing combinations of mutations in three regions of the metastable neutral-pH HA that are rearranged at fusion pH we obtain evidence for both additive and nonadditive effects and for an apparent order of dominance in the effects of amino acid substitutions in particular regions on the pH of fusion. We conclude that there are at least three components in the structural transition required for membrane fusion activity and consider possible pathways for the transition in relation to the known differences between neutral and fusion pH HA structures.

MeSH Terms
Aspartic Acid Glycine HeLa Cells Hemagglutinin Glycoproteins, Influenza Virus/biosynthesis,chemistry Humans Hydrogen-Ion Concentration Immunoblotting Liposomes Macromolecular Substances Membrane Fusion Models, Structural Mutagenesis, Site-Directed Point Mutation Protein Conformation Protein Structure, Secondary Recombinant Proteins/biosynthesis,chemistry Trypsin
Chemicals
Hemagglutinin Glycoproteins, Influenza Virus Liposomes Macromolecular Substances Recombinant Proteins Aspartic Acid Trypsin Glycine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Steinhauer D A
National Institute for Medical Research, Mill Hill, London, United Kingdom.
Martín J
Lin Y P
Wharton S A
Oldstone M B
Skehel J J
Wiley D C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.23.12873
Published
1996-11-12
Pages
12873-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24013
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.93.23.12873 PMC Full Text View journal details
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