Publication Date:
2016-05-13
Description:
The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N terminus of the Env-gp41 subunit, is a critical component of the virus-cell entry machinery. Here, we report the identification of a neutralizing antibody, N123-VRC34.01, which targets the fusion peptide and blocks viral entry by inhibiting conformational changes in gp120 and gp41 subunits of Env required for entry. Crystal structures of N123-VRC34.01 liganded to the fusion peptide, and to the full Env trimer, revealed an epitope consisting of the N-terminal eight residues of the gp41 fusion peptide and glycan N88 of gp120, and molecular dynamics showed that the N-terminal portion of the fusion peptide can be solvent-exposed. These results reveal the fusion peptide to be a neutralizing antibody epitope and thus a target for vaccine design. Authors: Rui Kong, Kai Xu, Tongqing Zhou, Priyamvada Acharya, Thomas Lemmin, Kevin Liu, Gabriel Ozorowski, Cinque Soto, Justin D. Taft, Robert T. Bailer, Evan M. Cale, Lei Chen, Chang W. Choi, Gwo-Yu Chuang, Nicole A. Doria-Rose, Aliaksandr Druz, Ivelin S. Georgiev, Jason Gorman, Jinghe Huang, M. Gordon Joyce, Mark K. Louder, Xiaochu Ma, Krisha McKee, Sijy O’Dell, Marie Pancera, Yongping Yang, Scott C. Blanchard, Walther Mothes, Dennis R. Burton, Wayne C. Koff, Mark Connors, Andrew B. Ward, Peter D. Kwong, John R. Mascola
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
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Chemistry and Pharmacology
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Geosciences
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Computer Science
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Medicine
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Natural Sciences in General
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Physics
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