9p98

Publication Abstract from PubMed

Integrins bind ligands between their alpha (alpha) and beta (beta) subunits and transmit signals through conformational changes. Early in chordate evolution, some alpha 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 alphaEbeta(7) integrin and the I domain-lacking alpha(4)beta(7) 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.

Molecular exaptation by the integrin alphaI domain.,Hollis JA, Chan MC, Malik HS, Campbell MG Sci Adv. 2025 Sep 12;11(37):eadx9567. doi: 10.1126/sciadv.adx9567. Epub 2025 Sep , 10. PMID:40929264^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.