Structure of influenza haemagglutinin at the pH of membrane fusion
Abstract
Low pH induces a conformational change in the influenza virus haemagglutinin, which then mediates fusion of the viral and host cell membranes. The three-dimensional structure of a fragment of the haemagglutinin in this conformation reveals a major refolding of the secondary and tertiary structure of the molecule. The apolar fusion peptide moves at least 100 A to one tip of the molecule. At the other end a helical segment unfolds, a subdomain relocates reversing the chain direction, and part of the structure becomes disordered.
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The HA stem region is highly conserved across all influenza A subtypes, and targeting this region can block the low-pH-induced conformational rearrangements associated with membrane fusion, which is essential for virus infection.
“The HA stem region is an attractive therapeutic epitope as it is highly conserved across all influenza A subtypes, and targeting this region can block the low-pH-induced conformational rearrangements associated with membrane fusion, which is essential for virus infection32,33.”
From Design of protein-binding proteins from the target structure alone (2022) · cites this paper as [32]
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- Authors
- Bullough, P. A., Hughson, F. M., Skehel, J. J., & Wiley, D. C.
- Affiliations
- Harvard University (US)
- National Institute for Medical Research (GB)
- Howard Hughes Medical Institute (US)
- Venue
- Nature
- Published
- 1994-09-01
- Volume
- 371
- Issue
- 6492
- Pages
- 37-43
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1978763290
- Cited by
- 1,564
- References
- 49
- Citations by year
- 2026: 19 · 2025: 16 · 2024: 22 · 2023: 22 · 2022: 30 · 2021: 32 · 2020: 39 · 2019: 25 · 2018: 44 · 2017: 29 · 2016: 39 · 2015: 43 · 2014: 58 · 2013: 54 · 2012: 49
- FWCI
- 72.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- influenza virus, hemagglutinin, membrane fusion, low pH, conformational change, fusion peptide, protein refolding, protein structure, structural disorder
- MeSH terms
- Amino Acid Sequence, Computer Graphics, Hemagglutinins, Viral, Hydrogen-Ion Concentration, Membrane Fusion, Molecular Sequence Data, Mutation, Orthomyxoviridae, Peptide Fragments, Protein Conformation, Protein Folding, Crystallography, X-Ray, Hemagglutinin Glycoproteins, Influenza Virus
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