Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody.
Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody.
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DOI：
10.1126/science.aae0474
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发表时间：
2016-05-13
期刊：
影响因子：
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通讯作者：
Mascola JR
中科院分区：
文献类型：
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作者：
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
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.
