EMD-8082

Single-particle
25.0 Å
EMD-8082 Deposition: 20/02/2016
Map released: 23/03/2016
Last modified: 06/11/2019
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-8082

BG505 SOSIP.664 HIV-1 Env trimer in complex with anti-HIV CH235 wk41 Fab

EMD-8082

Single-particle
25.0 Å
EMD-8082 Deposition: 20/02/2016
Map released: 23/03/2016
Last modified: 06/11/2019
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Human immunodeficiency virus 1, Homo sapiens
Sample: Complex containing 1 copy of CH235 wk41 anti-HIV Fab bound to a trimer of HIV-1 Env BG505 SOSIP.664

Deposition Authors: Ozorowski G, Ward AB
Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody.
PUBMED: 26949186
DOI: doi:10.1016/j.cell.2016.02.022
ISSN: 1097-4172
Abstract:
Antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a VH1-46-derived antibody lineage that matured to neutralize 90% of HIV-1 isolates. Structures of lineage antibodies CH235 (week 41 from time-of-infection, 18% breadth), CH235.9 (week 152, 77%), and CH235.12 (week 323, 90%) demonstrated the maturing epitope to focus on the conformationally invariant portion of the CD4bs. Similarities between CH235 lineage and five unrelated CD4bs lineages in epitope focusing, length-of-time to develop breadth, and extraordinary level of somatic hypermutation suggested commonalities in maturation among all CD4bs antibodies. Fortunately, the required CH235-lineage hypermutation appeared substantially guided by the intrinsic mutability of the VH1-46 gene, which closely resembled VH1-2. We integrated our CH235-lineage findings with a second broadly neutralizing lineage and HIV-1 co-evolution to suggest a vaccination strategy for inducing both lineages.