4um8 | pdb_00004um8
Crystal structure of alpha V beta 6
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 PubMedEight integrin alpha-beta heterodimers recognize ligands with an Arg-Gly-Asp (RGD) motif. However, the structural mechanism by which integrins differentiate among extracellular proteins with RGD motifs is not understood. Here, crystal structures, mutations and peptide-affinity measurements show that alphaVbeta6 binds with high affinity to a RGDLXXL/I motif within the prodomains of TGF-beta1 and TGF-beta3. The LXXL/I motif forms an amphipathic alpha-helix that binds in a hydrophobic pocket in the beta6 subunit. Elucidation of the basis for ligand binding specificity by the integrin beta subunit reveals contributions by three different betaI-domain loops, which we designate specificity-determining loops (SDLs) 1, 2 and 3. Variation in a pair of single key residues in SDL1 and SDL3 correlates with the variation of the entire beta subunit in integrin evolution, thus suggesting a paradigmatic role in overall beta-subunit function. Structural determinants of integrin beta-subunit specificity for latent TGF-beta,Dong X, Hudson NE, Lu C, Springer TA Nat Struct Mol Biol. 2014 Nov 10. doi: 10.1038/nsmb.2905. PMID:25383667[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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