Asymmetric recognition of HIV-1 Envelope trimer by V1V2 loop-targeting antibodies
- California Institute of Technology, United States
- 23andMe, United States
- Beth Israel Deaconess Medical Center, United States
- Tel Aviv University, Israel
- The Rockefeller University, United States
Abstract
The HIV-1 envelope (Env) glycoprotein binds to host cell receptors to mediate membrane fusion. The prefusion Env trimer is stabilized by V1V2 loops that interact at the trimer apex. Broadly neutralizing antibodies (bNAbs) against V1V2 loops, exemplified by PG9, bind asymmetrically as a single Fab to the apex of the symmetric Env trimer using a protruding CDRH3 to penetrate the Env glycan shield. Here we characterized a distinct mode of V1V2 epitope recognition by the new bNAb BG1 in which two Fabs bind asymmetrically per Env trimer using a compact CDRH3. Comparisons between cryo-EM structures of Env trimer complexed with BG1 (6.2Å resolution) and PG9 (11.5Å resolution) revealed a new V1V2-targeting strategy by BG1. Analyses of the EM structures provided information relevant to vaccine design including molecular details for different modes of asymmetric recognition of Env trimer and a binding model for BG1 recognition of V1V2 involving glycan flexibility.
Data availability
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BG1-Env-8ANC195 complexPublicly available at the EMBL_EBI Protein Dtat Bank in Europe (accession no: EMD-8693).
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PG9-Env-8ANC195 complexPublicly available at the EMBL_EBI Protein Dtat Bank in Europe (accession no: EMDB-8695).
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BG1 Fab coordinatePublicly available at the RCSB Protein Data Bank (accession no: 5VVF).
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BG1-Env-8ANC195 complex coordinatesPublicly available at the RCSB Protein Data Bank (accession no: 5VIY).
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PG9-Env-8ANC195 complex coordinatesPublicly available at the RCSB Protein Data Bank (accession no: 5VJ6).
Article and author information
Author details
Funding
National Institutes of Health (GM082545-06)
- Pamela J Bjorkman
National Institute of Allergy and Infectious Diseases (HIVRAD P01 AI100148)
- Michel C Nussenzweig
- Pamela J Bjorkman
Bill and Melinda Gates Foundation (1040753)
- Michel C Nussenzweig
- Pamela J Bjorkman
Comprehensive Antibody-Vaccine Immune Monitoring Consortium (1032144)
- Michael S Seaman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Arup K. Chakraborty, Massachusetts Institute of Technology, United States
Version history
- Received: April 1, 2017
- Accepted: May 24, 2017
- Accepted Manuscript published: May 26, 2017 (version 1)
- Version of Record published: June 15, 2017 (version 2)
Copyright
© 2017, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Asymmetric recognition of HIV-1 Envelope trimer by V1V2 loop-targeting antibodies
eLife 6:e27389.
https://doi.org/10.7554/eLife.27389
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