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2i9b

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(New page: 200px<br /> <applet load="2i9b" size="450" color="white" frame="true" align="right" spinBox="true" caption="2i9b, resolution 2.80&Aring;" /> '''Crystal structure o...)
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[[Image:2i9b.gif|left|200px]]<br />
 
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<applet load="2i9b" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2i9b, resolution 2.80&Aring;" />
 
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'''Crystal structure of ATF-urokinase receptor complex'''<br />
 
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==Overview==
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==Crystal structure of ATF-urokinase receptor complex==
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Recent studies indicate that binding of the urokinase-type plasminogen, activator (uPA) to its high-affinity receptor (uPAR) orchestrates uPAR, interactions with other cellular components that play a pivotal role in, diverse (patho-)physiological processes, including wound healing, angiogenesis, inflammation, and cancer metastasis. However, notwithstanding the wealth of biochemical data available describing the, activities of uPAR, little is known about the exact mode of uPAR/uPA, interactions or the presumed conformational changes that accompany, uPA/uPAR engagement. Here, we report the crystal structure of soluble, urokinase plasminogen activator receptor (suPAR), which contains the three, domains of the wild-type receptor but lacks the cell-surface anchoring, sequence, in complex with the amino-terminal fragment of urokinase-type, plasminogen activator (ATF), at the resolution of 2.8 A. We report the 1.9, A crystal structure of free ATF. Our results provide a structural basis, represented by conformational changes induced in uPAR, for several, published biochemical observations describing the nature of uPAR/uPA, interactions and provide insight into mechanisms that may be responsible, for the cellular responses induced by uPA binding.
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<StructureSection load='2i9b' size='340' side='right'caption='[[2i9b]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2i9b]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I9B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I9B FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2i9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i9b OCA], [https://pdbe.org/2i9b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i9b RCSB], [https://www.ebi.ac.uk/pdbsum/2i9b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i9b ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN] Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:[https://omim.org/entry/601709 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.<ref>PMID:20007542</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i9/2i9b_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2i9b ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Recent studies indicate that binding of the urokinase-type plasminogen activator (uPA) to its high-affinity receptor (uPAR) orchestrates uPAR interactions with other cellular components that play a pivotal role in diverse (patho-)physiological processes, including wound healing, angiogenesis, inflammation, and cancer metastasis. However, notwithstanding the wealth of biochemical data available describing the activities of uPAR, little is known about the exact mode of uPAR/uPA interactions or the presumed conformational changes that accompany uPA/uPAR engagement. Here, we report the crystal structure of soluble urokinase plasminogen activator receptor (suPAR), which contains the three domains of the wild-type receptor but lacks the cell-surface anchoring sequence, in complex with the amino-terminal fragment of urokinase-type plasminogen activator (ATF), at the resolution of 2.8 A. We report the 1.9 A crystal structure of free ATF. Our results provide a structural basis, represented by conformational changes induced in uPAR, for several published biochemical observations describing the nature of uPAR/uPA interactions and provide insight into mechanisms that may be responsible for the cellular responses induced by uPA binding.
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==Disease==
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Structural basis of interaction between urokinase-type plasminogen activator and its receptor.,Barinka C, Parry G, Callahan J, Shaw DE, Kuo A, Bdeir K, Cines DB, Mazar A, Lubkowski J J Mol Biol. 2006 Oct 20;363(2):482-95. Epub 2006 Aug 26. PMID:16979660<ref>PMID:16979660</ref>
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Known disease associated with this structure: Alzheimer disease, late-onset, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191840 191840]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2I9B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/U-plasminogen_activator U-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.73 3.4.21.73] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2I9B OCA].
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</div>
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<div class="pdbe-citations 2i9b" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Structural basis of interaction between urokinase-type plasminogen activator and its receptor., Barinka C, Parry G, Callahan J, Shaw DE, Kuo A, Bdeir K, Cines DB, Mazar A, Lubkowski J, J Mol Biol. 2006 Oct 20;363(2):482-95. Epub 2006 Aug 26. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16979660 16979660]
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*[[Urokinase 3D Structures|Urokinase 3D Structures]]
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*[[Urokinase plasminogen activator surface receptor 3D structures|Urokinase plasminogen activator surface receptor 3D structures]]
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*[[Urokinase receptor|Urokinase receptor]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: U-plasminogen activator]]
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[[Category: Barinka C]]
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[[Category: Barinka, C.]]
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[[Category: Lubkowski J]]
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[[Category: Lubkowski, J.]]
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[[Category: SO4]]
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[[Category: growth factor-like domain]]
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[[Category: kringle domain]]
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[[Category: urokinase receptor]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:42:36 2007''
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Current revision

Crystal structure of ATF-urokinase receptor complex

PDB ID 2i9b

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