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An internal ligand-bound, metastable state of a leukocyte integrin, aXb2An internal ligand-bound, metastable state of a leukocyte integrin, aXb2
Structural highlights
FunctionITAX_HUMAN Integrin alpha-X/beta-2 is a receptor for fibrinogen. It recognizes the sequence G-P-R in fibrinogen. It mediates cell-cell interaction during inflammatory responses. It is especially important in monocyte adhesion and chemotaxis. Publication Abstract from PubMedHow is massive conformational change in integrins achieved on a rapid timescale? We report crystal structures of a metastable, putative transition state of integrin alphaXbeta2. The alphaXbeta2 ectodomain is bent; however, a lattice contact stabilizes its ligand-binding alphaI domain in a high affinity, open conformation. Much of the alphaI alpha7 helix unwinds, loses contact with the alphaI domain, and reshapes to form an internal ligand that binds to the interface between the beta propeller and betaI domains. Lift-off of the alphaI domain above this platform enables a range of extensional and rotational motions without precedent in allosteric machines. Movements of secondary structure elements in the beta2 betaI domain occur in an order different than in beta3 integrins, showing that integrin beta subunits can be specialized to assume different intermediate states between closed and open. Mutations demonstrate that the structure trapped here is metastable and can enable rapid equilibration between bent and extended-open integrin conformations and up-regulation of leukocyte adhesiveness. An internal ligand-bound, metastable state of a leukocyte integrin, alphaXbeta2.,Sen M, Yuki K, Springer TA J Cell Biol. 2013 Nov 25;203(4):629-42. doi: 10.1083/jcb.201308083. PMID:24385486[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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