| Title: |
Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike |
| Authors: |
Lee, Jeong Hyun; Leaman, Daniel P.; Kim, Arthur S.; Torrents de la Peña, Alba; Sliepen, Kwinten; Yasmeen, Anila; Derking, Ronald; Ramos, Alejandra; de Taeye, Steven W.; Ozorowski, Gabriel; Klein, Florian; Burton, Dennis R.; Nussenzweig, Michel C.; Poignard, Pascal; Moore, John P.; Klasse, Per Johan; Sanders, Rogier W.; Zwick, Michael B.; Wilson, Ian A.; Ward, Andrew B. |
| Source: |
Nature Communications ; volume 6, issue 1 ; ISSN 2041-1723 |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2015 |
| Description: |
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 Å 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/ncomms9167 |
| Availability: |
https://doi.org/10.1038/ncomms9167; https://www.nature.com/articles/ncomms9167.pdf; https://www.nature.com/articles/ncomms9167 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| Accession Number: |
edsbas.D66699B7 |
| Database: |
BASE |