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Publication Abstract from PubMed

Integrin alphaVbeta8, which like alphaVbeta6 functions to activate TGF-betas, is atypical. Its beta8 subunit binds to a distinctive cytoskeleton adaptor and does not exhibit large changes in conformation upon binding to ligand. Here, crystal structures, hydrogen-deuterium exchange dynamics, and affinity measurements on mutants are used to compare alphaVbeta8 and alphaVbeta6. Lack of a binding site for one of three betaI domain divalent cations and a unique beta6-alpha7 loop conformation in beta8 facilitate movements of the alpha1 and alpha1' helices at the ligand binding pocket toward the high affinity state, without coupling to beta6-alpha7 loop reshaping and alpha7-helix pistoning that drive large changes in betaI domain-hybrid domain orientation seen in other integrins. Reciprocal swaps between beta6 and beta8 betaI domains increase affinity of alphaVbeta6 and decrease affinity of alphaVbeta8 and define features that regulate affinity of the betaI domain and its coupling to the hybrid domain.

General structural features that regulate integrin affinity revealed by atypical alphaVbeta8.,Wang J, Su Y, Iacob RE, Engen JR, Springer TA Nat Commun. 2019 Dec 2;10(1):5481. doi: 10.1038/s41467-019-13248-5. PMID:31792290^[1]

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