3u73

Crystal structure of stabilized human uPAR mutant in complex with ATFCrystal structure of stabilized human uPAR mutant in complex with ATF

Structural highlights 3u73 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Related: 2fat, 3bt1, 3bt2 Gene: MO3, PLAUR, UPAR (Homo sapiens), PLAU (Homo sapiens) Activity: U-plasminogen activator, with EC number 3.4.21.73 Resources: FirstGlance, OCA, RCSB, PDBsum Disease [UROK_HUMAN] Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:601709]. QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins. Function [UPAR_HUMAN] Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form. [UROK_HUMAN] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. Publication Abstract from PubMed The urokinase receptor urokinase-type plasminogen activator receptor (uPAR) is a surface receptor capable of not only focalizing urokinase-type plasminogen activator (uPA)-mediated fibrinolysis to the pericellular micro-environment but also promoting cell migration and chemotaxis. Consistent with this multifunctional role, uPAR binds several extracellular ligands, including uPA and vitronectin. Structural studies suggest that uPAR possesses structural flexibility. It is, however, not clear whether this flexibility is an inherent property of the uPAR structure per se or whether it is induced upon ligand binding. The crystal structure of human uPAR in its ligand-free state would clarify this issue, but such information remains unfortunately elusive. We now report the crystal structures of a stabilized, human uPAR (H47C/N259C) in its ligand-free form to 2.4 A and in complex with amino-terminal fragment (ATF) to 3.2 A. The structure of uPAR(H47C/N259C) in complex with ATF resembles the wild-type uPAR.ATF complex, demonstrating that these mutations do not perturb the uPA binding properties of uPAR. The present structure of uPAR(H47C/N259C) provides the first structural definition of uPAR in its ligand-free form, which represents one of the biologically active conformations of uPAR as defined by extensive biochemical studies. The domain boundary between uPAR DI-DII domains is more flexible than the DII-DIII domain boundary. Two important structural features are highlighted by the present uPAR structure. First, the DI-DIII domain boundary may face the cell membrane. Second, loop 130-140 of uPAR plays a dynamic role during ligand loading/unloading. Together, these studies provide new insights into uPAR structure-function relationships, emphasizing the importance of the inter-domain dynamics of this modular receptor. Crystal structure of the urokinase receptor in a ligand-free form.,Xu X, Gardsvoll H, Yuan C, Lin L, Ploug M, Huang M J Mol Biol. 2012 Mar 9;416(5):629-41. Epub 2012 Jan 21. PMID:22285761 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Urokinase

spinqualitylabelsall models 3u73, resolution 3.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image