9P99

CryoEM structure of integrin alphaEbeta7 bound to E-cadherin

Summary for 9P99

• Entry DOI: 10.2210/pdb9p99/pdb
• EMDB information: 71403
• Descriptor: Integrin alpha-E, Integrin beta-7, Cadherin-1, ... (8 entities in total)
• Functional Keywords: aeb7, gut adhesion, tissue residence, membrane receptor, cell adhesion
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 253715.80

Authors

Hollis, J.A.,Campbell, M.G. (deposition date: 2025-06-24, release date: 2025-09-24)

Primary citation

Hollis, J.A.,Chan, M.C.,Malik, H.S.,Campbell, M.G.
Molecular exaptation by the integrin alpha I domain.
Sci Adv, 11:eadx9567-eadx9567, 2025

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 integrin and the I domain-lacking αβ 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.

PubMed: 40929264
DOI: 10.1126/sciadv.adx9567

Experimental method

ELECTRON MICROSCOPY (3.37 Å)