{"doi":"10.1016/j.celrep.2025.115607","title":"Molecular basis of β2 integrin activation by talin unveils subunit-specific mechanisms of integrin signaling","abstract":"Integrins consist of 24 species, each with unique tissue expression profiles and distinct biological functions. The β subunit of integrin interacts with the FERM-folded head domain of talin through an NPxY/F motif, triggering integrin activation. Although this motif is conserved across most integrin-β subunits, the precise molecular mechanism governing talin's selective recognition of different integrin-β subunits remains unclear. We identify two distinct configurations of the talin head when interacting with β2 and β3 integrins, providing critical insights into subunit-specific recognition of integrins. Structural studies reveal that mutations at the subdomain interface of the talin head can shift its β2-bound configuration to a β3-bound configuration. This shift enhances β2-integrin affinity, leading to increased lymphocyte function-associated antigen-1 (LFA-1)-mediated natural killer cell activity. Together, our data elucidate the structural basis of talin's role in mediating integrin activation in a subunit-specific manner and advance our understanding of how talin may regulate diverse functions of various integrin species.","journal":"Cell Reports","year":2025,"id":529790,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9475,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":454467,"name":"Nicholas A. Maskalenko","orcid":"0000-0001-7690-5234","position":1,"is_corresponding":false},{"id":1409621,"name":"Salvin Kabir","orcid":null,"position":2,"is_corresponding":false},{"id":495333,"name":"Kerry S. Campbell","orcid":"0000-0003-4665-7326","position":3,"is_corresponding":false},{"id":407670,"name":"Jinhua Wu","orcid":"0000-0001-5913-0633","position":4,"is_corresponding":false},{"id":1005768,"name":"Tong Gao","orcid":"0000-0002-6879-7680","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T02:51:01.235017Z","pmid":"40310722","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":[]}