Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 616.9944 Other diseases
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2015
• Mô tả vật lý: Size: Article No. 8167 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 261065
• Chủ đề: 1. 60 applied life sciences; 2. Antibodies; 3. Cryoelectron microscopy; 4. Molecular biophysics; 5. X-ray crystallography

Tóm tắt

The recent identification of three broadly neutralizing antibodies (bnAbs) against gp120?gp41 interface epitopes has expanded the targetable surface on the HIV-1 envelope glycoprotein (Env) trimer. By using biochemical, biophysical and computational methods, we map the previously unknown trimer epitopes of two related antibodies, 3BC315 and 3BC176. A cryo-EM reconstruction of a soluble Env trimer bound to 3BC315 Fab at 9.3 � resolution reveals that the antibody binds between two gp41 protomers, and neutralizes the virus by accelerating trimer decay. In contrast, bnAb 35O22 binding to a partially overlapping quaternary epitope at the gp120?gp41 interface does not induce decay. A conserved gp41-proximal glycan at N88 was also shown to play a role in the binding kinetics of 3BC176 and 3BC315. Finally, our data suggest that the dynamic structure of the Env trimer influences exposure of bnAb epitopes.