5AWN

Crystal structure of Human anti-HIV-1 broadly neutralizing antibody 3BC176 Fab

Summary for 5AWN

• Entry DOI: 10.2210/pdb5awn/pdb
• Related: 5CCK
• Descriptor: Heavy chain of 3BC176 Fab, Light chain of 3BC176 Fab (3 entities in total)
• Functional Keywords: hiv-1, env, broadly neutralizing antibody, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 48132.87

Authors

Lee, J.H.,Wilson, I.A.,Ward, A.B. (deposition date: 2015-07-06, release date: 2015-11-11, Last modification date: 2024-10-23)

Primary citation

Lee, J.H.,Leaman, D.P.,Kim, A.S.,Torrents de la Pena, A.,Sliepen, K.,Yasmeen, A.,Derking, R.,Ramos, A.,de Taeye, S.W.,Ozorowski, G.,Klein, F.,Burton, D.R.,Nussenzweig, M.C.,Poignard, P.,Moore, J.P.,Klasse, P.J.,Sanders, R.W.,Zwick, M.B.,Wilson, I.A.,Ward, A.B.
Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike.
Nat Commun, 6:8167-8167, 2015

PubMed Abstract: 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.

PubMed: 26404402
DOI: 10.1038/ncomms9167

Experimental method

X-RAY DIFFRACTION (1.887 Å)