Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody.

TitleFusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody.
Publication TypeJournal Article
Year of Publication2016
AuthorsKong R, Xu K, Zhou T, Acharya P, Lemmin T, Liu K, Ozorowski G, Soto C, Taft JD, Bailer RT, Cale EM, Chen L, Choi CW, Chuang G-Y, Doria-Rose NA, Druz A, Georgiev IS, Gorman J, Huang J, M Joyce G, Louder MK, Ma X, McKee K, O'Dell S, Pancera M, Yang Y, Blanchard SC, Mothes W, Burton DR, Koff WC, Connors M, Ward AB, Kwong PD, Mascola JR
JournalScience
Volume352
Issue6287
Pagination828-33
Date Published05/13/2016
ISSN1095-9203
KeywordsAIDS Vaccines, Amino Acid Sequence, Antibodies, Neutralizing, Antibodies, Viral, B-Lymphocytes, Crystallography, X-Ray, HIV Envelope Protein gp120, HIV Envelope Protein gp41, HIV-1, Humans, Hydrophobic and Hydrophilic Interactions, Immunodominant Epitopes, Molecular Sequence Data, Peptides, Protein Conformation, Viral Fusion Proteins, Virus Internalization
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.

DOI10.1126/science.aae0474
Alternate JournalScience
PubMed ID27174988
PubMed Central IDPMC4917739
Grant ListUM1 AI100663 / AI / NIAID NIH HHS / United States
P01GM56550 / GM / NIGMS NIH HHS / United States
R01 GM116654 / GM / NIGMS NIH HHS / United States
P01 GM056550 / GM / NIGMS NIH HHS / United States
R01GM079238 / GM / NIGMS NIH HHS / United States
/ / Intramural NIH HHS / United States
R01 CA098727 / CA / NCI NIH HHS / United States
R01GM116654 / GM / NIGMS NIH HHS / United States
R01 GM079238 / GM / NIGMS NIH HHS / United States
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