6djp
Integrin alpha-v beta-8 in complex with the Fabs 8B8 and 68
Structural highlights
FunctionITAV_HUMAN The alpha-V integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. Publication Abstract from PubMedIntegrins are conformationally flexible cell surface receptors that survey the extracellular environment for their cognate ligands. Interactions with ligands are thought to be linked to global structural rearrangements involving transitions between bent, extended-closed and extended-open forms. Thus far, structural details are lacking for integrins in the extended conformations due to extensive flexibility between the headpiece and legs in this conformation. Here we present single-particle electron cryomicroscopy structures of human alphavbeta8 integrin in the extended-closed conformation, which has been considered to be a low-affinity intermediate. Our structures show the headpiece rotating about a flexible alphav knee, suggesting a ligand surveillance mechanism for integrins in their extended-closed form. Our model predicts that the extended conformation is mainly stabilized by an interface formed between flexible loops in the upper and lower domains of the alphav leg. Confirming these findings with the alphavbeta3 integrin suggests that our model of stabilizing the extended-closed conformation is generalizable to other integrins. Cryo-EM structure of the alphavbeta8 integrin reveals a mechanism for stabilizing integrin extension.,Cormier A, Campbell MG, Ito S, Wu S, Lou J, Marks J, Baron JL, Nishimura SL, Cheng Y Nat Struct Mol Biol. 2018 Aug;25(8):698-704. doi: 10.1038/s41594-018-0093-x. Epub, 2018 Jul 30. PMID:30061598[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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