Structure of HIV-1 gp41 with its membrane anchors targeted by neutralizing antibodies
- Univ. Grenoble Alpes, France
- University of the Basque Country, Biofisika Institute, Spain
- University of Zurich, Switzerland
- Université de Lorraine, France
- University of Lorraine, France
Abstract
The HIV-1 gp120/gp41 trimer undergoes a series of conformational changes in order to catalyze gp41-induced fusion of viral and cellular membranes. Here, we present the crystal structure of gp41 locked in a fusion intermediate state by an MPER-specific neutralizing antibody. The structure illustrates the conformational plasticity of the six membrane anchors arranged asymmetrically with the fusion peptides and the transmembrane regions pointing into different directions. Hinge regions located adjacent to the fusion peptide and the transmembrane region facilitate the conformational flexibility that allows high affinity binding of broadly neutralizing anti-MPER antibodies. Molecular dynamics simulation of the MPER Ab-stabilized gp41 conformation reveals a possible transition pathway into the final post-fusion conformation with the central fusion peptides forming a hydrophobic core with flanking transmembrane regions. This suggests that MPER-specific broadly neutralizing antibodies can block final steps of refolding of the fusion peptide and the transmembrane region, which is required for completing membrane fusion.
Data availability
Diffraction data have been deposited in PDB under the accession code 7AEJ.All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Table 2.
Article and author information
Author details
Christophe J Chipot
Winfried Weissenhorn
Funding
H2020 Health (681137)
- Winfried Weissenhorn
Agence Nationale de la Recherche (ANR-17-EURE-0003)
- Winfried Weissenhorn
Ministerio de Economía, Industria y Competitividad, Gobierno de España (BIO2015-64421-R)
- Jose L Nieva
Ministerio de Ciencia, Innovación y Universidades (RTI2018-095624-B-C21)
- Jose L Nieva
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Christophe 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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Structure of HIV-1 gp41 with its membrane anchors targeted by neutralizing antibodies
eLife 10:e65005.
https://doi.org/10.7554/eLife.65005
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