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

Kong 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 GY, Doria-Rose NA, Druz A, Georgiev IS, Gorman J, Huang J, Joyce MG, 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
Science. 2016 352 (6287): 828-33

PMID: 27174988 · PMCID: PMC4917739 · DOI:10.1126/science.aae0474

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.

Copyright © 2016, American Association for the Advancement of Science.

MeSH Terms (17)

AIDS Vaccines Amino Acid Sequence Antibodies, Neutralizing Antibodies, Viral B-Lymphocytes Crystallography, X-Ray HIV-1 HIV Envelope Protein gp41 HIV Envelope Protein gp120 Humans Hydrophobic and Hydrophilic Interactions Immunodominant Epitopes Molecular Sequence Data Peptides Protein Conformation Viral Fusion Proteins Virus Internalization

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