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2i9b

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Revision as of 08:25, 18 October 2017

Crystal structure of ATF-urokinase receptor complex

Structural highlights

2i9b is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	2i9a
Gene:	PLAU (HUMAN), PLAUR, MO3, UPAR (HUMAN)
Activity:	U-plasminogen activator, with EC number 3.4.21.73
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.^[1]

Function

[UROK_HUMAN] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. [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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Paterson AD, Rommens JM, Bharaj B, Blavignac J, Wong I, Diamandis M, Waye JS, Rivard GE, Hayward CP. Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene. Blood. 2010 Feb 11;115(6):1264-6. doi: 10.1182/blood-2009-07-233965. Epub 2009, Dec 9. PMID:20007542 doi:10.1182/blood-2009-07-233965
↑ Barinka C, Parry G, Callahan J, Shaw DE, Kuo A, Bdeir K, Cines DB, Mazar A, Lubkowski J. Structural basis of interaction between urokinase-type plasminogen activator and its receptor. J Mol Biol. 2006 Oct 20;363(2):482-95. Epub 2006 Aug 26. PMID:16979660 doi:10.1016/j.jmb.2006.08.063

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2i9b"

@@ Line 1: / Line 1: @@
 ==Crystal structure of ATF-urokinase receptor complex==
 <StructureSection load='2i9b' size='340' side='right' caption='[[2i9b]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2i9b]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2I9B FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2i9a|2i9a]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLAU ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PLAUR, MO3, UPAR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2i9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i9b OCA], [http://pdbe.org/2i9b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2i9b RCSB], [http://www.ebi.ac.uk/pdbsum/2i9b PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2i9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i9b OCA], [http://pdbe.org/2i9b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2i9b RCSB], [http://www.ebi.ac.uk/pdbsum/2i9b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2i9b ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 32: / Line 33: @@
 </div>
 <div class="pdbe-citations 2i9b" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Urokinase|Urokinase]]
 == References ==
 <references/>

2i9b

From Proteopedia

Revision as of 08:25, 18 October 2017

Crystal structure of ATF-urokinase receptor complex

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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