ArticleMolecular biology of the cell2000
A point mutation in the transmembrane domain of the hemagglutinin of influenza virus stabilizes a hemifusion intermediate that can transit to fusion.
Article in Molecular biology of the cell, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed.
- Article
- Computational methods to study enveloped viral entry.Biochemical Society transactions · 2021Review
- Safety, Immunogenicity, and Protective Efficacy of a Chimeric A/B Live Attenuated Influenza Vaccine in a Mouse Model.Microorganisms · 2021Article
- Cholesterol Binding to the Transmembrane Region of a Group 2 Hemagglutinin (HA) of Influenza Virus Is Essential for Virus Replication, Affecting both Virus Assembly and HA Fusion Activity.Journal of virology · 2019Article
- Influenza hemagglutinin membrane anchor.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Transmembrane Domains of Highly Pathogenic Viral Fusion Proteins Exhibit Trimeric AssociationmSphere · 2018Article
- Structure of the Ebola virus envelope protein MPER/TM domain and its interaction with the fusion loop explains their fusion activity.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Hendra virus fusion protein transmembrane domain contributes to pre-fusion protein stability.The Journal of biological chemistry · 2017Article
- SM protein Munc18-2 facilitates transition of Syntaxin 11-mediated lipid mixing to complete fusion for T-lymphocyte cytotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Interfering With Lipid Raft Association: A Mechanism to Control Influenza Virus Infection ByIranian journal of pharmaceutical research : IJPR · 2017Article
- The Interaction between Influenza HA Fusion Peptide and Transmembrane Domain Affects Membrane Structure.Biophysical journal · 2015Article
- The transmembrane domain peptide of vesicular stomatitis virus promotes both intermediate and pore formation during PEG-mediated vesicle fusion.Biophysical journal · 2014Article
- Evidences for the existence of intermolecular disulfide-bonded oligomers in the H3 hemagglutinins expressed in insect cells.Virus genes · 2014Article
- Trimeric transmembrane domain interactions in paramyxovirus fusion proteins: roles in protein folding, stability, and function.The Journal of biological chemistry · 2013Article
- A novel single virus infection system reveals that influenza virus preferentially infects cells in g1 phase.PloS one · 2013Article
- Review
- Beyond anchoring: the expanding role of the hendra virus fusion protein transmembrane domain in protein folding, stability, and function.Journal of virology · 2012Article
- Line-tension controlled mechanism for influenza fusion.PloS one · 2012Article
- The final conformation of the complete ectodomain of the HA2 subunit of influenza hemagglutinin can by itself drive low pH-dependent fusion.The Journal of biological chemistry · 2011Article
- The transmembrane domain sequence affects the structure and function of the Newcastle disease virus fusion protein.Journal of virology · 2011Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
A hemagglutinin (HA) of influenza virus having a single semiconserved Gly residue within the transmembrane domain mutated to Leu (G520L) was expressed on cells; these cells were bound to red blood cells. By decreasing pH at 23 degrees C rather than 37 degrees C, an intermediate with properties expected of hemifusion just as the membranes are about to transit to full fusion was captured. As evidence: 1) increasing temperature to 37 degrees C at neutral pH allowed fusion to proceed; 2) after achieving the intermediate, the two membranes did not separate from each other after proteolytic cleavage of G520L because cells treated with proteinase K could not fuse upon temperature increase but could fuse upon the addition of chlorpromazine; and 3) at the point of the intermediate, adding exogenous lipids known to promote or inhibit the creation of hemifusion did not significantly alter the lipid dye spread that occurred upon increasing temperature, implying that at the intermediate, contacting membrane leaflets had already merged. A stable intermediate of hemifusion that could transit to fusion was also generated for wild-type HA, but pH had to be reduced at the significantly lower temperature of 4 degrees C. The fusion pores generated by G520L did not enlarge, whereas those induced by wild-type HA did. The finding that a state of transitional hemifusion can be readily obtained via a point mutation without the need for unusually low temperature supports the hypothesis that hemifusion occurs before pore formation.
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