| Literature DB >> 27174988 |
Rui Kong1, Kai Xu1, Tongqing Zhou1, Priyamvada Acharya1, Thomas Lemmin2, Kevin Liu1, Gabriel Ozorowski3, Cinque Soto1, Justin D Taft1, Robert T Bailer1, Evan M Cale1, Lei Chen1, Chang W Choi1, Gwo-Yu Chuang1, Nicole A Doria-Rose1, Aliaksandr Druz1, Ivelin S Georgiev1, Jason Gorman1, Jinghe Huang4, M Gordon Joyce1, Mark K Louder1, Xiaochu Ma5, Krisha McKee1, Sijy O'Dell1, Marie Pancera1, Yongping Yang1, Scott C Blanchard6, Walther Mothes5, Dennis R Burton7, Wayne C Koff8, Mark Connors4, Andrew B Ward3, Peter D Kwong9, John R Mascola9.
Abstract
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.Entities:
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Year: 2016 PMID： 27174988 PMCID： PMC4917739 DOI： 10.1126/science.aae0474
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728