5EWI

Crystal Structure of the Human Fab VRC38.01, an HIV-1 V1V2-Directed Neutralizing Antibody Isolated from Donor N90

Summary for 5EWI

• Entry DOI: 10.2210/pdb5ewi/pdb
• Descriptor: VRC38.01 Heavy Chain, VRC38.01 Light Chain (3 entities in total)
• Functional Keywords: fab, hiv-1, v1v2, env, antibody, envelope, neutralizing, immune system
• Biological source: Homo sapiens; More
• Cellular location: Secreted : P01834
• Total number of polymer chains: 2
• Total formula weight: 49275.12

Authors

Gorman, J.,Kwong, P.D. (deposition date: 2015-11-20, release date: 2016-11-23, Last modification date: 2024-11-06)

Primary citation

Cale, E.M.,Gorman, J.,Radakovich, N.A.,Crooks, E.T.,Osawa, K.,Tong, T.,Li, J.,Nagarajan, R.,Ozorowski, G.,Ambrozak, D.R.,Asokan, M.,Bailer, R.T.,Bennici, A.K.,Chen, X.,Doria-Rose, N.A.,Druz, A.,Feng, Y.,Joyce, M.G.,Louder, M.K.,O'Dell, S.,Oliver, C.,Pancera, M.,Connors, M.,Hope, T.J.,Kepler, T.B.,Wyatt, R.T.,Ward, A.B.,Georgiev, I.S.,Kwong, P.D.,Mascola, J.R.,Binley, J.M.
Virus-like Particles Identify an HIV V1V2 Apex-Binding Neutralizing Antibody that Lacks a Protruding Loop.
Immunity, 46:777-791.e10, 2017

PubMed Abstract: Most HIV-1-specific neutralizing antibodies isolated to date exhibit unusual characteristics that complicate their elicitation. Neutralizing antibodies that target the V1V2 apex of the HIV-1 envelope (Env) trimer feature unusually long protruding loops, which enable them to penetrate the HIV-1 glycan shield. As antibodies with loops of requisite length are created through uncommon recombination events, an alternative mode of apex binding has been sought. Here, we isolated a lineage of Env apex-directed neutralizing antibodies, N90-VRC38.01-11, by using virus-like particles and conformationally stabilized Env trimers as B cell probes. A crystal structure of N90-VRC38.01 with a scaffolded V1V2 revealed a binding mode involving side-chain-to-side-chain interactions that reduced the distance the antibody loop must traverse the glycan shield, thereby facilitating V1V2 binding via a non-protruding loop. The N90-VRC38 lineage thus identifies a solution for V1V2-apex binding that provides a more conventional B cell pathway for vaccine design.

PubMed: 28514685
DOI: 10.1016/j.immuni.2017.04.011

Experimental method

X-RAY DIFFRACTION (1.5996 Å)