5hj2

Integrin alpha2beta1 I-domain

spinqualitylabelsall models 5hj2, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5hj2 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.153Å Ligands: CA, CL, GOL, PEG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ITA2_HUMAN Integrin alpha-2/beta-1 is a receptor for laminin, collagen, collagen C-propeptides, fibronectin and E-cadherin. It recognizes the proline-hydroxylated sequence G-F-P-G-E-R in collagen. It is responsible for adhesion of platelets and other cells to collagens, modulation of collagen and collagenase gene expression, force generation and organization of newly synthesized extracellular matrix. Publication Abstract from PubMed Integrins are transmembrane cell-extracellular matrix adhesion receptors that impact many cellular functions. A subgroup of integrins contain an inserted (I) domain within the alpha-subunits (alphaI) that mediate ligand recognition where function is contingent on binding a divalent cation at the metal ion dependent adhesion site (MIDAS). Ca(2+) is reported to promote alpha1I but inhibit alpha2I ligand binding. We co-crystallized individual I-domains with MIDAS-bound Ca(2+) and report structures at 1.4 and 2.15 A resolution, respectively. Both structures are in the "closed" ligand binding conformation where Ca(2+) induces minimal global structural changes. Comparisons with Mg(2+)-bound structures reveal Mg(2+) and Ca(2+) bind alpha1I in a manner sufficient to promote ligand binding. In contrast, Ca(2+) is displaced in the alpha2I domain MIDAS by 1.4 A relative to Mg(2+) and unable to directly coordinate all MIDAS residues. We identified an E152-R192 salt bridge hypothesized to limit the flexibility of the alpha2I MIDAS, thus, reducing Ca(2+) binding. A alpha2I E152A construct resulted in a 10,000-fold increase in Mg(2+) and Ca(2+) binding affinity while increasing binding to collagen ligands 20%. These data indicate the E152-R192 salt bridge is a key distinction in the molecular mechanism of differential ion binding of these two I domains. Salt-bridge modulates differential calcium-mediated ligand binding to integrin alpha1- and alpha2-I domains.,Brown KL, Banerjee S, Feigley A, Abe H, Blackwell TS, Pozzi A, Hudson BG, Zent R Sci Rep. 2018 Feb 13;8(1):2916. doi: 10.1038/s41598-018-21231-1. PMID:29440721 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Integrin 3D structures

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