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| | ==Crystal structure of murine thrombin in complex with the extracellular fragment of murine PAR3== | | ==Crystal structure of murine thrombin in complex with the extracellular fragment of murine PAR3== |
| - | <StructureSection load='2pux' size='340' side='right' caption='[[2pux]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='2pux' size='340' side='right'caption='[[2pux]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2pux]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PUX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PUX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2pux]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PUX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PUX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1shh|1shh]], [[2ocv|2ocv]], [[2pv9|2pv9]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1shh|1shh]], [[2ocv|2ocv]], [[2pv9|2pv9]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">F2, Cf2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">F2, Cf2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=2pux FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pux OCA], [http://pdbe.org/2pux PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2pux RCSB], [http://www.ebi.ac.uk/pdbsum/2pux PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2pux ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2pux FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pux OCA], [https://pdbe.org/2pux PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pux RCSB], [https://www.ebi.ac.uk/pdbsum/2pux PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pux ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/THRB_MOUSE THRB_MOUSE]] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing (By similarity). [[http://www.uniprot.org/uniprot/PAR3_MOUSE PAR3_MOUSE]] High affinity receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation. | + | [[https://www.uniprot.org/uniprot/THRB_MOUSE THRB_MOUSE]] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing (By similarity). [[https://www.uniprot.org/uniprot/PAR3_MOUSE PAR3_MOUSE]] High affinity receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Thrombin|Thrombin]] | + | *[[Thrombin 3D Structures|Thrombin 3D Structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Lk3 transgenic mice]] | | [[Category: Lk3 transgenic mice]] |
| | [[Category: Bah, A]] | | [[Category: Bah, A]] |
| Structural highlights
Function
[THRB_MOUSE] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing (By similarity). [PAR3_MOUSE] High affinity receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation.
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
It has been proposed that the cleaved form of protease-activated receptor 3 (PAR3) acts as a cofactor for thrombin cleavage and activation of PAR4 on murine platelets, but the molecular basis of this physiologically important effect remains elusive. X-ray crystal structures of murine thrombin bound to extracellular fragments of the murine receptors PAR3 ((38)SFNGGPQNTFEEFPLSDIE(56)) and PAR4 ((51)KSSDKPNPR downward arrow GYPGKFCANDSDTLELPASSQA(81), downward arrow = site of cleavage) have been solved at 2.0 and 3.5 A resolution, respectively. The cleaved form of PAR3, traced in the electron density maps from Gln-44 to Glu-56, makes extensive hydrophobic and electrostatic contacts with exosite I of thrombin through the fragment (47)FEEFPLSDIE(56). Occupancy of exosite I by PAR3 allosterically changes the conformation of the 60-loop and shifts the position of Trp-60d approximately 10 A with a resulting widening of the access to the active site. The PAR4 fragment, traced entirely in the electron density maps except for five C-terminal residues, clamps Trp-60d, Tyr-60a, and the aryl-binding site of thrombin with Pro-56 and Pro-58 at the P2 and P4 positions and engages the primary specificity pocket with Arg-59. The fragment then leaves the active site with Gly-60 and folds into a short helical turn that directs the backbone away from exosite I and over the autolysis loop. The structures demonstrate that thrombin activation of PAR4 may occur with exosite I available to bind cofactor molecules, like the cleaved form of PAR3, whose function is to promote substrate diffusion into the active site by allosterically changing the conformation of the 60-loop.
Crystal structures of murine thrombin in complex with the extracellular fragments of murine protease-activated receptors PAR3 and PAR4.,Bah A, Chen Z, Bush-Pelc LA, Mathews FS, Di Cera E Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11603-8. Epub 2007 Jul 2. PMID:17606903[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bah A, Chen Z, Bush-Pelc LA, Mathews FS, Di Cera E. Crystal structures of murine thrombin in complex with the extracellular fragments of murine protease-activated receptors PAR3 and PAR4. Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11603-8. Epub 2007 Jul 2. PMID:17606903
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