Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Science (American Association for the Advancement of Science), 2016-05, Vol.352 (6287), p.828-833

Ort / Verlag

United States: American Association for the Advancement of Science

Erscheinungsjahr

2016

Link zum Volltext

Quelle

American Association for the Advancement of Science

Beschreibungen/Notizen

• 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.