1jln
From Proteopedia
(New page: 200px<br /><applet load="1jln" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jln, resolution 1.81Å" /> '''Crystal structure of...) |
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| - | [[Image:1jln.gif|left|200px]]<br /><applet load="1jln" size=" | + | [[Image:1jln.gif|left|200px]]<br /><applet load="1jln" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1jln, resolution 1.81Å" /> | caption="1jln, resolution 1.81Å" /> | ||
'''Crystal structure of the catalytic domain of protein tyrosine phosphatase PTP-SL/BR7'''<br /> | '''Crystal structure of the catalytic domain of protein tyrosine phosphatase PTP-SL/BR7'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Protein tyrosine phosphatases PTP-SL and PTPBR7 are isoforms belonging to | + | Protein tyrosine phosphatases PTP-SL and PTPBR7 are isoforms belonging to cytosolic membrane-associated and to receptor-like PTPs (RPTPs), respectively. They represent a new family of PTPs with a major role in activation and translocation of MAP kinases. Specifically, the complex formation between PTP-SL and ERK2 involves an unusual interaction leading to the phosphorylation of PTP-SL by ERK2 at Thr253 and the inactivating dephosphorylation of ERK2 by PTP-SL. This interaction is strictly dependent upon a kinase interaction motif (KIM) (residues 224-239) situated at the N terminus of the PTP-SL catalytic domain. We report the first crystal structure of the catalytic domain for a member of this family (PTP-SL, residues 254-549, identical with residues 361-656 of PTPBR7), providing an example of an RPTP with single cytoplasmic domain, which is monomeric, having an unhindered catalytic site. In addition to the characteristic PTP-core structure, PTP-SL has an N-terminal helix, possibly orienting the KIM motif upon interaction with the target ERK2. An unusual residue in the catalytically important WPD loop promotes formation of a hydrophobically and electrostatically stabilised clamp. This could induce increased rigidity to the WPD loop and therefore reduced catalytic activity, in agreement with our kinetic measurements. A docking model based on the PTP-SL structure suggests that, in the complex with ERK2, the phosphorylation of PTP-SL should be accomplished first. The subsequent dephosphorylation of ERK2 seems to be possible only if a conformational rearrangement of the two interacting partners takes place. |
==About this Structure== | ==About this Structure== | ||
| - | 1JLN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] Full crystallographic information is available from [http:// | + | 1JLN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JLN OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein-tyrosine-phosphatase]] | [[Category: Protein-tyrosine-phosphatase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Aricescu, A | + | [[Category: Aricescu, A R.]] |
| - | [[Category: Fulga, T | + | [[Category: Fulga, T A.]] |
[[Category: Renault, L.]] | [[Category: Renault, L.]] | ||
| - | [[Category: Scheidig, A | + | [[Category: Scheidig, A J.]] |
| - | [[Category: Szedlacsek, S | + | [[Category: Szedlacsek, S E.]] |
[[Category: erk2-map kinase regulation]] | [[Category: erk2-map kinase regulation]] | ||
[[Category: protein tyrosine phosphatase]] | [[Category: protein tyrosine phosphatase]] | ||
| Line 24: | Line 24: | ||
[[Category: ptpbr7]] | [[Category: ptpbr7]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:24:03 2008'' |
Revision as of 11:24, 21 February 2008
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Crystal structure of the catalytic domain of protein tyrosine phosphatase PTP-SL/BR7
Overview
Protein tyrosine phosphatases PTP-SL and PTPBR7 are isoforms belonging to cytosolic membrane-associated and to receptor-like PTPs (RPTPs), respectively. They represent a new family of PTPs with a major role in activation and translocation of MAP kinases. Specifically, the complex formation between PTP-SL and ERK2 involves an unusual interaction leading to the phosphorylation of PTP-SL by ERK2 at Thr253 and the inactivating dephosphorylation of ERK2 by PTP-SL. This interaction is strictly dependent upon a kinase interaction motif (KIM) (residues 224-239) situated at the N terminus of the PTP-SL catalytic domain. We report the first crystal structure of the catalytic domain for a member of this family (PTP-SL, residues 254-549, identical with residues 361-656 of PTPBR7), providing an example of an RPTP with single cytoplasmic domain, which is monomeric, having an unhindered catalytic site. In addition to the characteristic PTP-core structure, PTP-SL has an N-terminal helix, possibly orienting the KIM motif upon interaction with the target ERK2. An unusual residue in the catalytically important WPD loop promotes formation of a hydrophobically and electrostatically stabilised clamp. This could induce increased rigidity to the WPD loop and therefore reduced catalytic activity, in agreement with our kinetic measurements. A docking model based on the PTP-SL structure suggests that, in the complex with ERK2, the phosphorylation of PTP-SL should be accomplished first. The subsequent dephosphorylation of ERK2 seems to be possible only if a conformational rearrangement of the two interacting partners takes place.
About this Structure
1JLN is a Single protein structure of sequence from Mus musculus. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Full crystallographic information is available from OCA.
Reference
Crystal structure of PTP-SL/PTPBR7 catalytic domain: implications for MAP kinase regulation., Szedlacsek SE, Aricescu AR, Fulga TA, Renault L, Scheidig AJ, J Mol Biol. 2001 Aug 17;311(3):557-68. PMID:11493009
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