EMD-23424

Single-particle
4.8 Å
EMD-23424 Deposition: 04/02/2021
Map released: 02/06/2021
Last modified: 20/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-23424

Cryo-EM map of Q23.17_DS-SOSIP in complex with Glycan276-Dependent Broadly Neutralizing Antibody 179NC75 Fab

EMD-23424

Single-particle
4.8 Å
EMD-23424 Deposition: 04/02/2021
Map released: 02/06/2021
Last modified: 20/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Human immunodeficiency virus 1, Homo sapiens
Sample: Trimeric HIV-1 Env in complex with VRC33.01 Fab
Fitted models: 7llk (Avg. Q-score: 0.236)

Deposition Authors: Manne K , Acharya P
Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies.
PUBMED: 34731616
DOI: doi:10.1016/j.celrep.2021.109922
ISSN: 2211-1247
Abstract:
Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. To understand how this glycan can be recognized, here we isolate two lineages of glycan276-dependent CD4bs antibodies. Antibody CH540-VRC40.01 (named for donor-lineage.clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. By contrast, glycan276-independent CD4bs antibodies, such as VRC01, displace glycan276 upon binding. These results provide a foundation for understanding antibody recognition of glycan276 and suggest its presence may be crucial for priming immunogens seeking to initiate broad CD4bs recognition.