2ouh
From Proteopedia
(New page: 200px<br /><applet load="2ouh" size="350" color="white" frame="true" align="right" spinBox="true" caption="2ouh, resolution 2.4Å" /> '''Crystal structure of ...) |
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caption="2ouh, resolution 2.4Å" /> | caption="2ouh, resolution 2.4Å" /> | ||
'''Crystal structure of the Thrombospondin-1 N-terminal domain in complex with fractionated Heparin DP10'''<br /> | '''Crystal structure of the Thrombospondin-1 N-terminal domain in complex with fractionated Heparin DP10'''<br /> | ||
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| + | ==Overview== | ||
| + | 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. | ||
==About this Structure== | ==About this Structure== | ||
| - | 2OUH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OUH OCA]. | + | 2OUH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Sites: <scene name='pdbsite=AC1:So4+Binding+Site+For+Residue+A+248'>AC1</scene>, <scene name='pdbsite=AC2:So4+Binding+Site+For+Residue+A+249'>AC2</scene>, <scene name='pdbsite=AC3:So4+Binding+Site+For+Residue+A+250'>AC3</scene>, <scene name='pdbsite=AC4:So4+Binding+Site+For+Residue+B+248'>AC4</scene>, <scene name='pdbsite=AC5:So4+Binding+Site+For+Residue+B+249'>AC5</scene> and <scene name='pdbsite=AC6:So4+Binding+Site+For+Residue+B+250'>AC6</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OUH OCA]. |
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| + | ==Reference== | ||
| + | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18065761 18065761] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: tspn-1]] | [[Category: tspn-1]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:22:43 2008'' |
Revision as of 16:22, 21 February 2008
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Crystal structure of the Thrombospondin-1 N-terminal domain in complex with fractionated Heparin DP10
Overview
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.
About this Structure
2OUH is a Single protein structure of sequence from Homo sapiens with as ligand. Known structural/functional Sites: , , , , and . Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 18:22:43 2008
Categories: Homo sapiens | Single protein | Joachimiak, A. | Lawler, J. | Tan, K. | Wang, J. | SO4 | Cell adhesion | Dp10 | Fractionated heparin | Hbd | Tsp-1 | Tspn-1
