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A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin
Influenza virus hemagglutinin (HA) mediates receptor binding and viral entry during influenza infection. The development of receptor analogs as viral entry blockers has not been successful, suggesting that sialic acid may not be an ideal scaffold to obtain broad and potent HA inhibitors. Here we rep...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594569/ https://www.ncbi.nlm.nih.gov/pubmed/23396351 http://dx.doi.org/10.1038/nsmb.2500 |
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author | Xu, Rui Krause, Jens C. McBride, Ryan Paulson, James C. Crowe, James E. Wilson, Ian A. |
author_facet | Xu, Rui Krause, Jens C. McBride, Ryan Paulson, James C. Crowe, James E. Wilson, Ian A. |
author_sort | Xu, Rui |
collection | PubMed |
description | Influenza virus hemagglutinin (HA) mediates receptor binding and viral entry during influenza infection. The development of receptor analogs as viral entry blockers has not been successful, suggesting that sialic acid may not be an ideal scaffold to obtain broad and potent HA inhibitors. Here we report crystal structures of Fab fragments from three human antibodies that neutralize the 1957 pandemic H2N2 influenza virus in complex with H2 HA. All three antibodies use an aromatic residue to plug a conserved cavity in the HA receptor-binding site. Each antibody interacts with the absolutely conserved HA1 Trp153 at the cavity base through π-π stacking with the signature Phe54 of two V(H)1-69 antibodies or a tyrosine from HCDR3 in the other antibody. This remarkably conserved interaction can be used as a starting point to design inhibitors targeting this conserved hydrophobic pocket in influenza viruses. |
format | Online Article Text |
id | pubmed-3594569 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-35945692013-09-01 A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin Xu, Rui Krause, Jens C. McBride, Ryan Paulson, James C. Crowe, James E. Wilson, Ian A. Nat Struct Mol Biol Article Influenza virus hemagglutinin (HA) mediates receptor binding and viral entry during influenza infection. The development of receptor analogs as viral entry blockers has not been successful, suggesting that sialic acid may not be an ideal scaffold to obtain broad and potent HA inhibitors. Here we report crystal structures of Fab fragments from three human antibodies that neutralize the 1957 pandemic H2N2 influenza virus in complex with H2 HA. All three antibodies use an aromatic residue to plug a conserved cavity in the HA receptor-binding site. Each antibody interacts with the absolutely conserved HA1 Trp153 at the cavity base through π-π stacking with the signature Phe54 of two V(H)1-69 antibodies or a tyrosine from HCDR3 in the other antibody. This remarkably conserved interaction can be used as a starting point to design inhibitors targeting this conserved hydrophobic pocket in influenza viruses. 2013-02-10 2013-03 /pmc/articles/PMC3594569/ /pubmed/23396351 http://dx.doi.org/10.1038/nsmb.2500 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Xu, Rui Krause, Jens C. McBride, Ryan Paulson, James C. Crowe, James E. Wilson, Ian A. A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin |
title | A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin |
title_full | A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin |
title_fullStr | A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin |
title_full_unstemmed | A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin |
title_short | A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin |
title_sort | recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594569/ https://www.ncbi.nlm.nih.gov/pubmed/23396351 http://dx.doi.org/10.1038/nsmb.2500 |
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