{"doi":"10.1016/j.cell.2024.04.049","title":"Ligand binding initiates single-molecule integrin conformational activation","abstract":"Integrins link the extracellular environment to the actin cytoskeleton in cell migration and adhesiveness. Rapid coordination between events outside and inside the cell is essential. Single-molecule fluorescence dynamics show that ligand binding to the bent-closed integrin conformation, which predominates on cell surfaces, is followed within milliseconds by two concerted changes, leg extension and headpiece opening, to give the high-affinity integrin conformation. The extended-closed integrin conformation is not an intermediate but can be directly accessed from the extended-open conformation and provides a pathway for ligand dissociation. In contrast to ligand, talin, which links the integrin β-subunit cytoplasmic domain to the actin cytoskeleton, modestly stabilizes but does not induce extension or opening. Integrin activation is thus initiated by outside-in signaling and followed by inside-out signaling. Our results further imply that talin binding is insufficient for inside-out integrin activation and that tensile force transmission through the ligand-integrin-talin-actin cytoskeleton complex is required.","journal":"Cell","year":2024,"id":417650,"datarank":0.6284482113039639,"base_score":4.189654742026425,"endowment":4.189654742026425,"self_citation_contribution":0.6284482113039639,"citation_network_contribution":0.0,"self_endowment_contribution":0.6284482113039639,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":65,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9469,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":467231,"name":"Myung Hyun Jo","orcid":"0000-0003-2745-2843","position":1,"is_corresponding":false},{"id":396628,"name":"Jiabin Yan","orcid":null,"position":2,"is_corresponding":false},{"id":1077992,"name":"Taylor Hall","orcid":"0000-0002-8268-3575","position":3,"is_corresponding":false},{"id":577468,"name":"Joon Lee","orcid":"0000-0003-3887-8540","position":4,"is_corresponding":false},{"id":518158,"name":"Uriel López-Sánchez","orcid":"0000-0003-4937-7055","position":5,"is_corresponding":false},{"id":1204820,"name":"S. Betty Yan","orcid":null,"position":6,"is_corresponding":false},{"id":22168,"name":"Taekjip Ha","orcid":"0000-0003-2195-6258","position":7,"is_corresponding":false},{"id":395798,"name":"Timothy A. Springer","orcid":"0000-0001-6627-2904","position":8,"is_corresponding":false},{"id":238231,"name":"Jing Li","orcid":"0000-0001-5697-9527","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:56:56.807779Z","pmid":"38772370","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":[]}