Evolutionary origin and structural ligand mimicry by the inserted domain of alpha-integrin proteins.

ABSTRACT: Heterodimeric integrin proteins transmit signals through conformational changes upon ligand binding between their alpha (α) and beta (β) subunits. Early in chordate evolution, some α subunits acquired an "inserted" (I) domain, which expanded their ligand binding capacity but simultaneously obstructed the ancestral ligand-binding pocket. While this would seemingly impede conventional ligand-mediated integrin activation, it was proposed that the I domain itself could serve both as a ligand replacement and an activation trigger. Here, we provide compelling evidence in support of this longstanding hypothesis using high-resolution cryo-electron microscopy structures of two distinct integrin complexes: the ligand-free and E-cadherin-bound states of the αEβ7 integrin with the I domain, as well as

SUBMITTER: Hollis JA 

PROVIDER: S-EPMC10659397 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature