Publication Date:
2016-05-14
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kong, Rui -- Xu, Kai -- Zhou, Tongqing -- Acharya, Priyamvada -- Lemmin, Thomas -- Liu, Kevin -- Ozorowski, Gabriel -- Soto, Cinque -- Taft, Justin D -- Bailer, Robert T -- Cale, Evan M -- Chen, Lei -- Choi, Chang W -- Chuang, Gwo-Yu -- Doria-Rose, Nicole A -- Druz, Aliaksandr -- Georgiev, Ivelin S -- Gorman, Jason -- Huang, Jinghe -- Joyce, M Gordon -- Louder, Mark K -- Ma, Xiaochu -- McKee, Krisha -- O'Dell, Sijy -- Pancera, Marie -- Yang, Yongping -- Blanchard, Scott C -- Mothes, Walther -- Burton, Dennis R -- Koff, Wayne C -- Connors, Mark -- Ward, Andrew B -- Kwong, Peter D -- Mascola, John R -- P01GM56550/GM/NIGMS NIH HHS/ -- R01GM079238/GM/NIGMS NIH HHS/ -- R01GM116654/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2016 May 13;352(6287):828-33. doi: 10.1126/science.aae0474.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ; Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA. ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. ; HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA. ; Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, NY 10021, USA. ; Department of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA 02142, USA. ; International AIDS Vaccine Initiative, New York, NY 10038, USA. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. pdkwong@nih.gov jmascola@nih.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27174988" target="_blank"〉PubMed〈/a〉
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
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Chemistry and Pharmacology
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Computer Science
,
Medicine
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Natural Sciences in General
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Physics
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