{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["11(37)"],"submitter":["Hollis JA"],"pubmed_abstract":["Integrins bind ligands between their alpha (α) and beta (β) subunits and transmit signals through conformational changes. Early in chordate evolution, some α subunits acquired an \"inserted\" (I) domain that expanded integrin's ligand-binding repertoire but obstructed the ancestral ligand pocket, seemingly blocking conventional integrin activation. Here, we compare cryo-electron microscopy structures of apo and ligand-bound states of the I domain-containing αEβ<sub>7</sub> integrin and the I domain-lacking α<sub>4</sub>β<sub>7</sub> integrin to illuminate how the I domain intrinsically mimics an extrinsic ligand to preserve integrin function. We trace the I domain's evolutionary origin to an ancestral collagen-collagen interaction domain, identifying an ancient molecular exaptation that facilitated integrin activation immediately upon I domain insertion. Our analyses reveal the evolutionary and biochemical basis of expanded cellular communication in vertebrates."],"journal":["Science advances"],"pagination":["eadx9567"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12422189"],"repository":["biostudies-literature"],"pubmed_title":["Molecular exaptation by the integrin αI domain."],"pmcid":["PMC12422189"],"pubmed_authors":["Campbell MG","Chan MC","Malik HS","Hollis JA"],"additional_accession":[]},"is_claimable":false,"name":"Molecular exaptation by the integrin αI domain.","description":"Integrins bind ligands between their alpha (α) and beta (β) subunits and transmit signals through conformational changes. Early in chordate evolution, some α subunits acquired an \"inserted\" (I) domain that expanded integrin's ligand-binding repertoire but obstructed the ancestral ligand pocket, seemingly blocking conventional integrin activation. Here, we compare cryo-electron microscopy structures of apo and ligand-bound states of the I domain-containing αEβ<sub>7</sub> integrin and the I domain-lacking α<sub>4</sub>β<sub>7</sub> integrin to illuminate how the I domain intrinsically mimics an extrinsic ligand to preserve integrin function. We trace the I domain's evolutionary origin to an ancestral collagen-collagen interaction domain, identifying an ancient molecular exaptation that facilitated integrin activation immediately upon I domain insertion. Our analyses reveal the evolutionary and biochemical basis of expanded cellular communication in vertebrates.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-03T05:44:50.457Z","creation":"2026-04-25T03:14:29.581Z"},"accession":"S-EPMC12422189","cross_references":{"pubmed":["40929264"],"doi":["10.1126/sciadv.adx9567"]}}