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Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env
HIV’s envelope glycoprotein (Env) is the sole target for neutralizing antibodies. The structures of many broadly neutralizing antibodies (bNAbs) in complex with truncated Env subunits or components have been reported. However, their interaction with the intact Env trimer, and the structural determin...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338595/ https://www.ncbi.nlm.nih.gov/pubmed/25652336 http://dx.doi.org/10.1038/ncomms7144 |
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author | Guttman, Miklos Cupo, Albert Julien, Jean-Philippe Sanders, Rogier W. Wilson, Ian A. Moore, John P. Lee, Kelly K. |
author_facet | Guttman, Miklos Cupo, Albert Julien, Jean-Philippe Sanders, Rogier W. Wilson, Ian A. Moore, John P. Lee, Kelly K. |
author_sort | Guttman, Miklos |
collection | PubMed |
description | HIV’s envelope glycoprotein (Env) is the sole target for neutralizing antibodies. The structures of many broadly neutralizing antibodies (bNAbs) in complex with truncated Env subunits or components have been reported. However, their interaction with the intact Env trimer, and the structural determinants that underlie neutralization resistance in this more native context are less well understood. Here we use hydrogen/deuterium-exchange to examine the interactions between a panel of bNAbs and native-like Env trimers (SOSIP.664 trimers). Highly potent bNAbs cause only localized effects at their binding interface, while the binding of less potent antibodies is associated with elaborate changes throughout the trimer. In conjunction with binding kinetics, our results suggest that poorly neutralizing antibodies can only bind when the trimer transiently samples an open state. We propose that the kinetics of such opening motions varies among isolates, with Env from neutralization-sensitive viruses opening more frequently than Env from resistant viruses. |
format | Online Article Text |
id | pubmed-4338595 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-43385952015-08-05 Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env Guttman, Miklos Cupo, Albert Julien, Jean-Philippe Sanders, Rogier W. Wilson, Ian A. Moore, John P. Lee, Kelly K. Nat Commun Article HIV’s envelope glycoprotein (Env) is the sole target for neutralizing antibodies. The structures of many broadly neutralizing antibodies (bNAbs) in complex with truncated Env subunits or components have been reported. However, their interaction with the intact Env trimer, and the structural determinants that underlie neutralization resistance in this more native context are less well understood. Here we use hydrogen/deuterium-exchange to examine the interactions between a panel of bNAbs and native-like Env trimers (SOSIP.664 trimers). Highly potent bNAbs cause only localized effects at their binding interface, while the binding of less potent antibodies is associated with elaborate changes throughout the trimer. In conjunction with binding kinetics, our results suggest that poorly neutralizing antibodies can only bind when the trimer transiently samples an open state. We propose that the kinetics of such opening motions varies among isolates, with Env from neutralization-sensitive viruses opening more frequently than Env from resistant viruses. 2015-02-05 /pmc/articles/PMC4338595/ /pubmed/25652336 http://dx.doi.org/10.1038/ncomms7144 Text en Users may view, print, copy, and download 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 Guttman, Miklos Cupo, Albert Julien, Jean-Philippe Sanders, Rogier W. Wilson, Ian A. Moore, John P. Lee, Kelly K. Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env |
title | Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env |
title_full | Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env |
title_fullStr | Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env |
title_full_unstemmed | Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env |
title_short | Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env |
title_sort | antibody potency relates to the ability to recognize the closed, pre-fusion form of hiv env |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338595/ https://www.ncbi.nlm.nih.gov/pubmed/25652336 http://dx.doi.org/10.1038/ncomms7144 |
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