EMD-23424
Cryo-EM map of Q23.17_DS-SOSIP in complex with Glycan276-Dependent Broadly Neutralizing Antibody 179NC75 Fab
EMD-23424
Single-particle4.8 Å
![EMD-23424](https://www.ebi.ac.uk/emdb/images/entry/EMD-23424/400_23424.gif)
Map released: 02/06/2021
Last modified: 20/11/2024
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
Sample: Trimeric HIV-1 Env in complex with VRC33.01 Fab
Fitted models: 7llk (Avg. Q-score: 0.236)
Deposition Authors: Manne K
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies.
Cottrell CA
,
Manne K
,
Kong R,
Wang S
,
Zhou T
,
Chuang GY,
Edwards RJ
,
Henderson R,
Janowska K,
Kopp M,
Lin BC,
Louder MK,
Olia AS,
Rawi R,
Shen CH,
Taft JD,
Torres JL,
Wu NR,
Zhang B,
Doria-Rose NA,
Cohen MS,
Haynes BF,
Shapiro L,
Ward AB,
Acharya P,
Mascola JR,
Kwong PD
(2021) Cell Rep , 37 , 109922 - 109922
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
(2021) Cell Rep , 37 , 109922 - 109922
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.
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.