6msu | pdb_00006msu

Integrin alphaVBeta3 in complex with EETI-II 2.5F

spinqualitylabelsall models 6msu, resolution 3.11Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6msu is a 3 chain structure with sequence from Ecballium elaterium and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.11Å Ligands: BMA, CL, MAN, MN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ITAV_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 PubMed Targeting both integrins alphaVbeta3 and alpha5beta1 simultaneously appears to be more effective in cancer therapy than targeting each one alone. The structural requirements for bispecific binding of ligand to integrins have not been fully elucidated. RGD-containing knottin 2.5F binds selectively to alphaVbeta3 and alpha5beta1, whereas knottin 2.5D is alphaVbeta3 specific. To elucidate the structural basis of this selectivity, we determined the structures of 2.5F and 2.5D as apo proteins and in complex with alphaVbeta3, and compared their interactions with integrins using molecular dynamics simulations. These studies show that 2.5D engages alphaVbeta3 by an induced fit, but conformational selection of a flexible RGD loop accounts for high-affinity selective binding of 2.5F to both integrins. The contrasting binding of the highly flexible low-affinity linear RGD peptides to multiple integrins suggests that a "Goldilocks zone" of conformational flexibility of the RGD loop in 2.5F underlies its selective binding promiscuity to integrins. Structural Basis of the Differential Binding of Engineered Knottins to Integrins alphaVbeta3 and alpha5beta1.,Van Agthoven JF, Shams H, Cochran FV, Alonso JL, Kintzing JR, Garakani K, Adair BD, Xiong JP, Mofrad MRK, Cochran JR, Arnaout MA Structure. 2019 Sep 3;27(9):1443-1451.e6. doi: 10.1016/j.str.2019.06.011. Epub, 2019 Jul 25. PMID:31353240 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Integrin 3D structures

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