{"doi":"10.1016/j.jbc.2022.101819","title":"Antigenic analysis of the HIV-1 envelope trimer implies small differences between structural states 1 and 2","abstract":"The conformationally dynamic HIV-1 envelope trimer (Env) is the target of broadly neutralizing antibodies (bnAbs) that block viral entry. Single-molecule Förster resonance energy transfer (smFRET) has revealed that HIV-1 Env exists in at least three conformational states on the virion. Prior to complete host-receptor engagement (State 3), Env resides most prevalently in the smFRET-defined State 1, which is preferentially recognized by most bnAbs that are elicited by natural infection. smFRET has also revealed that soluble trimers containing prefusion-stabilizing disulfide and isoleucine-to-proline substitutions reside primarily in State 2, which is a required intermediate between States 1 and 3. While high-resolution Env structures have been determined for States 2 and 3, the structure of these trimers in State 1 is unknown. To provide insight into the State 1 structure, here we characterized antigenic differences between smFRET-defined states and then correlated these differences with known structural differences between States 2 and 3. We found that cell surface-expressed Env was enriched in each state using state-enriching antibody fragments or small-molecule virus entry inhibitors and then assessed binding to HIV-1 bnAbs preferentially binding different states. We observed small but consistent differences in binding between Env enriched in States 1 and 2, and a more than 10-fold difference in binding to Env enriched in these states versus Env enriched in State 3. We conclude that structural differences between HIV-1 Env States 1 and 3 are likely more than 10-fold greater than those between States 1 and 2, providing important insight into State 1.","journal":"Journal of Biological Chemistry","year":2022,"id":260767,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":914934,"name":"Jefferson I. Driscoll","orcid":null,"position":1,"is_corresponding":false},{"id":615584,"name":"Myungjin Lee","orcid":"0000-0002-4972-3811","position":2,"is_corresponding":false},{"id":105630,"name":"Jason Gorman","orcid":"0000-0002-3775-6560","position":3,"is_corresponding":false},{"id":105631,"name":"Tongqing Zhou","orcid":"0000-0002-3935-4637","position":4,"is_corresponding":false},{"id":241923,"name":"Maolin Lu","orcid":"0000-0002-8099-6447","position":5,"is_corresponding":false},{"id":280562,"name":"Hui Geng","orcid":"0000-0002-7389-6931","position":6,"is_corresponding":false},{"id":457173,"name":"Yen‐Ting Lai","orcid":"0000-0003-3700-6417","position":7,"is_corresponding":false},{"id":229149,"name":"Gwo‐Yu Chuang","orcid":"0000-0003-0375-1013","position":8,"is_corresponding":false},{"id":105605,"name":"Nicole A. Doria‐Rose","orcid":"0000-0002-5731-3054","position":9,"is_corresponding":false},{"id":241931,"name":"Walther Mothes","orcid":"0000-0002-3367-7240","position":10,"is_corresponding":false},{"id":105633,"name":"Peter D. Kwong","orcid":"0000-0003-3560-232X","position":11,"is_corresponding":false},{"id":105614,"name":"John R. Mascola","orcid":"0000-0002-5293-4695","position":12,"is_corresponding":false},{"id":601085,"name":"Evan M. Cale","orcid":"0000-0002-9176-8263","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T00:26:07.666421Z","pmid":"35283191","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}