{"doi":"10.1016/j.celrep.2021.109922","title":"Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies","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.","journal":"Cell Reports","year":2021,"id":161658,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":231056,"name":"Kartik Manne","orcid":"0000-0002-7218-4852","position":1,"is_corresponding":false},{"id":323753,"name":"Rui Kong","orcid":"0000-0003-1779-5885","position":2,"is_corresponding":false},{"id":229157,"name":"Shuishu Wang","orcid":"0000-0002-0865-4522","position":3,"is_corresponding":false},{"id":105631,"name":"Tongqing Zhou","orcid":"0000-0002-3935-4637","position":4,"is_corresponding":false},{"id":229149,"name":"Gwo‐Yu Chuang","orcid":"0000-0003-0375-1013","position":5,"is_corresponding":false},{"id":227358,"name":"Robert J. 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