'''Crystal structure of the catalytic domain of protein tyrosine phosphatase PTP-SL/BR7'''
===Crystal structure of the catalytic domain of protein tyrosine phosphatase PTP-SL/BR7===
==Overview==
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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.
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==About this Structure==
==About this Structure==
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[[Category: Ptp-sl]]
[[Category: Ptp-sl]]
[[Category: Ptpbr7]]
[[Category: Ptpbr7]]
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Revision as of 17:26, 1 July 2008
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1JLN is a Single protein structure of sequence from Mus musculus. 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
