Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody.
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.
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, G-Y; 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
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