2ouh: Difference between revisions
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< | ==Crystal structure of the Thrombospondin-1 N-terminal domain in complex with fractionated Heparin DP10== | ||
<StructureSection load='2ouh' size='340' side='right'caption='[[2ouh]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2ouh]] is a 2 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=2OUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OUH FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=2ouh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ouh OCA], [https://pdbe.org/2ouh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ouh RCSB], [https://www.ebi.ac.uk/pdbsum/2ouh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ouh ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TSP1_HUMAN TSP1_HUMAN] Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Binds heparin. May play a role in dentinogenesis and/or maintenance of dentin and dental pulp (By similarity). Ligand for CD36 mediating antiangiogenic properties.<ref>PMID:11134179</ref> <ref>PMID:15014436</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ou/2ouh_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=2ouh ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Through its interactions with proteins and proteoglycans, thrombospondin-1 (TSP-1) functions at the interface of the cell membrane and the extracellular matrix to regulate matrix structure and cellular phenotype. We have previously determined the structure of the high affinity heparin-binding domain of TSP-1, designated TSPN-1, in association with the synthetic heparin, Arixtra. To establish that the binding of TSPN-1 to Arixtra is representative of the association with naturally occurring heparins, we have determined the structures of TSPN-1 in complex with heparin oligosaccharides containing eight (dp8) and ten (dp10) subunits, by x-ray crystallography. We have found that dp8 and dp10 bind to TSPN-1 in a manner similar to Arixtra and that dp8 and dp10 induce the formation of trans and cis TSPN-1 dimers, respectively. In silico docking calculations partnered with our crystal structures support the importance of arginine residues in positions 29, 42, and 77 in binding sulfate groups of the dp8 and dp10 forms of heparin. The ability of several TSPN-1 domains to bind to glycosaminoglycans simultaneously probably increases the affinity of binding through multivalent interactions. The formation of cis and trans dimers of the TSPN-1 domain with relatively short segments of heparin further enhances the ability of TSP-1 to participate in high affinity binding to glycosaminoglycans. Dimer formation may also involve TSPN-1 domains from two separate TSP-1 molecules. This association would enable glycosaminoglycans to cluster TSP-1. | |||
Heparin-induced cis- and trans-dimerization modes of the thrombospondin-1 N-terminal domain.,Tan K, Duquette M, Liu JH, Shanmugasundaram K, Joachimiak A, Gallagher JT, Rigby AC, Wang JH, Lawler J J Biol Chem. 2008 Feb 15;283(7):3932-41. Epub 2007 Dec 7. PMID:18065761<ref>PMID:18065761</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2ouh" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Thrombospondin|Thrombospondin]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Joachimiak | [[Category: Joachimiak A]] | ||
[[Category: Lawler | [[Category: Lawler J]] | ||
[[Category: Tan | [[Category: Tan K]] | ||
[[Category: Wang | [[Category: Wang J]] | ||
Latest revision as of 10:44, 9 October 2024
Crystal structure of the Thrombospondin-1 N-terminal domain in complex with fractionated Heparin DP10Crystal structure of the Thrombospondin-1 N-terminal domain in complex with fractionated Heparin DP10
Structural highlights
FunctionTSP1_HUMAN Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Binds heparin. May play a role in dentinogenesis and/or maintenance of dentin and dental pulp (By similarity). Ligand for CD36 mediating antiangiogenic properties.[1] [2] 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 PubMedThrough its interactions with proteins and proteoglycans, thrombospondin-1 (TSP-1) functions at the interface of the cell membrane and the extracellular matrix to regulate matrix structure and cellular phenotype. We have previously determined the structure of the high affinity heparin-binding domain of TSP-1, designated TSPN-1, in association with the synthetic heparin, Arixtra. To establish that the binding of TSPN-1 to Arixtra is representative of the association with naturally occurring heparins, we have determined the structures of TSPN-1 in complex with heparin oligosaccharides containing eight (dp8) and ten (dp10) subunits, by x-ray crystallography. We have found that dp8 and dp10 bind to TSPN-1 in a manner similar to Arixtra and that dp8 and dp10 induce the formation of trans and cis TSPN-1 dimers, respectively. In silico docking calculations partnered with our crystal structures support the importance of arginine residues in positions 29, 42, and 77 in binding sulfate groups of the dp8 and dp10 forms of heparin. The ability of several TSPN-1 domains to bind to glycosaminoglycans simultaneously probably increases the affinity of binding through multivalent interactions. The formation of cis and trans dimers of the TSPN-1 domain with relatively short segments of heparin further enhances the ability of TSP-1 to participate in high affinity binding to glycosaminoglycans. Dimer formation may also involve TSPN-1 domains from two separate TSP-1 molecules. This association would enable glycosaminoglycans to cluster TSP-1. Heparin-induced cis- and trans-dimerization modes of the thrombospondin-1 N-terminal domain.,Tan K, Duquette M, Liu JH, Shanmugasundaram K, Joachimiak A, Gallagher JT, Rigby AC, Wang JH, Lawler J J Biol Chem. 2008 Feb 15;283(7):3932-41. Epub 2007 Dec 7. PMID:18065761[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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