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Yorodumi- SASDFC2: Urokinase plasminogen activator surface receptor, uPAR K50C-V70C,... -
+Open data
-Basic information
Entry | Database: SASBDB / ID: SASDFC2 |
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Sample | Urokinase plasminogen activator surface receptor, uPAR K50C-V70C, complex with urokinase-type plasminogen activator (Amino Terminal Fragment, ATF).
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Function / homology | Function and homology information urokinase plasminogen activator receptor activity / Attachment of GPI anchor to uPAR / positive regulation of homotypic cell-cell adhesion / negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway / u-plasminogen activator / regulation of smooth muscle cell-matrix adhesion / urokinase plasminogen activator signaling pathway / regulation of plasminogen activation / regulation of fibrinolysis / regulation of wound healing ...urokinase plasminogen activator receptor activity / Attachment of GPI anchor to uPAR / positive regulation of homotypic cell-cell adhesion / negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway / u-plasminogen activator / regulation of smooth muscle cell-matrix adhesion / urokinase plasminogen activator signaling pathway / regulation of plasminogen activation / regulation of fibrinolysis / regulation of wound healing / protein complex involved in cell-matrix adhesion / regulation of proteolysis / negative regulation of plasminogen activation / regulation of smooth muscle cell migration / regulation of signaling receptor activity / serine-type endopeptidase complex / Dissolution of Fibrin Clot / smooth muscle cell migration / positive regulation of epidermal growth factor receptor signaling pathway / extrinsic component of membrane / plasminogen activation / positive regulation of DNA binding / positive regulation of release of cytochrome c from mitochondria / regulation of cell adhesion mediated by integrin / tertiary granule membrane / negative regulation of fibrinolysis / regulation of cell adhesion / specific granule membrane / negative regulation of intrinsic apoptotic signaling pathway / serine protease inhibitor complex / fibrinolysis / cell projection / chemotaxis / blood coagulation / signaling receptor activity / regulation of cell population proliferation / response to hypoxia / positive regulation of cell migration / positive regulation of protein phosphorylation / protein domain specific binding / endoplasmic reticulum lumen / external side of plasma membrane / serine-type endopeptidase activity / signaling receptor binding / focal adhesion / Neutrophil degranulation / endoplasmic reticulum membrane / negative regulation of apoptotic process / enzyme binding / cell surface / signal transduction / proteolysis / extracellular space / extracellular exosome / extracellular region / membrane / plasma membrane Similarity search - Function |
Biological species | Homo sapiens (human) |
Citation | Journal: J Biol Chem / Year: 2019 Title: Did evolution create a flexible ligand-binding cavity in the urokinase receptor through deletion of a plesiotypic disulfide bond? Authors: Julie M Leth / Haydyn D T Mertens / Katrine Zinck Leth-Espensen / Thomas J D Jørgensen / Michael Ploug / Abstract: The urokinase receptor (uPAR) is a founding member of a small protein family with multiple Ly6/uPAR (LU) domains. The motif defining these LU domains contains five plesiotypic disulfide bonds ...The urokinase receptor (uPAR) is a founding member of a small protein family with multiple Ly6/uPAR (LU) domains. The motif defining these LU domains contains five plesiotypic disulfide bonds stabilizing its prototypical three-fingered fold having three protruding loops. Notwithstanding the detailed knowledge on structure-function relationships in uPAR, one puzzling enigma remains unexplored. Why does the first LU domain in uPAR (DI) lack one of its consensus disulfide bonds, when the absence of this particular disulfide bond impairs the correct folding of other single LU domain-containing proteins? Here, using a variety of contemporary biophysical methods, we found that reintroducing the two missing half-cystines in uPAR DI caused the spontaneous formation of the corresponding consensus 7-8 LU domain disulfide bond. Importantly, constraints due to this cross-link impaired (i) the binding of uPAR to its primary ligand urokinase and (ii) the flexible interdomain assembly of the three LU domains in uPAR. We conclude that the evolutionary deletion of this particular disulfide bond in uPAR DI may have enabled the assembly of a high-affinity urokinase-binding cavity involving all three LU domains in uPAR. Of note, an analogous neofunctionalization occurred in snake venom α-neurotoxins upon loss of another pair of the plesiotypic LU domain half-cystines. In summary, elimination of the 7-8 consensus disulfide bond in the first LU domain of uPAR have significant functional and structural consequences. |
Contact author |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Data source
SASBDB page | SASDFC2 |
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-Related structure data
Related structure data | C: citing same article (ref.) |
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Similar structure data |
-External links
Related items in Molecule of the Month |
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-Models
Model #2811 | Type: dummy / Radius of dummy atoms: 3.00 A Comment: Refined DAMMIN model from average volume (10 DAMMIF iterations) Chi-square value: 1.433 Search similar-shape structures of this assembly by Omokage search (details) |
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-Sample
Sample | Name: Urokinase plasminogen activator surface receptor, uPAR K50C-V70C, complex with urokinase-type plasminogen activator (Amino Terminal Fragment, ATF). Specimen concentration: 0.30-2.50 / Entity id: 66 / 1481 |
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Buffer | Name: 20 mM PBS, 5 %(v/v) glycerol / pH: 7.4 |
Entity #66 | Name: uPAR / Type: protein Description: Urokinase plasminogen activator surface receptor Formula weight: 36.98 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: Q03405 Sequence: MGHPPLLPLL LLLHTCVPAS WGLRCMQCKT NGDCRVEECA LGQDLCRTTI VRLWEEGEEL ELVEKSCTHS EKTNRTLSYR TGLKITSLTE VVCGLDLCNQ GNSGRAVTYS RSRYLECISC GSSDMSCERG RHQSLQCRSP EEQCLDVVTH WIQEGEEGRP KDDRHLRGCG ...Sequence: MGHPPLLPLL LLLHTCVPAS WGLRCMQCKT NGDCRVEECA LGQDLCRTTI VRLWEEGEEL ELVEKSCTHS EKTNRTLSYR TGLKITSLTE VVCGLDLCNQ GNSGRAVTYS RSRYLECISC GSSDMSCERG RHQSLQCRSP EEQCLDVVTH WIQEGEEGRP KDDRHLRGCG YLPGCPGSNG FHNNDTFHFL KCCNTTKCNE GPILELENLP QNGRQCYSCK GNSTHGCSSE ETFLIDCRGP MNQCLVATGT HEPKNQSYMV RGCATASMCQ HAHLGDAFSM NHIDVSCCTK SGCNHPDLDV QYRSGAAPQP GPAHLSLTIT LLMTARLWGG TLLWT |
Entity #1481 | Name: ATF / Type: protein Description: Urokinase-type plasminogen activator (Amino Terminal Fragment) Formula weight: 16.099 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: P00749 Sequence: MRALLARLLL CVLVVSDSKG SNELHQVPSN CDCLNGGTCV SNKYFSNIHW CNCPKKFGGQ HCEIDKSKTC YEGNGHFYRG KASTDTMGRP CLPWNSATVL QQTYHAHRSD ALQLGLGKHN YCRNPDNRRR PWCYVQVGLK PLV |
-Experimental information
Beam | Instrument name: PETRA III EMBL P12 / City: Hamburg / 国: Germany / Type of source: X-ray synchrotron / Wavelength: 0.124 Å / Dist. spec. to detc.: 3.1 mm | |||||||||||||||||||||||||||||||||||||||
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Detector | Name: Pilatus 2M | |||||||||||||||||||||||||||||||||||||||
Scan | Title: Urokinase plasminogen activator surface receptor, uPAR K50C-V70C, complex with urokinase-type plasminogen activator (Amino Terminal Fragment, ATF). Measurement date: May 5, 2017 / Storage temperature: 10 °C / Cell temperature: 10 °C / Exposure time: 0.05 sec. / Number of frames: 20 / Unit: 1/nm /
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Distance distribution function P(R) | Sofotware P(R): GNOM 5.0 / Number of points: 1074 /
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Result | Type of curve: extrapolated Comments: Introduced disulfide in the first LU domain, DI, of uPAR (K50C-V70C).
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