1JLN

Crystal structure of the catalytic domain of protein tyrosine phosphatase PTP-SL/BR7

Summary for 1JLN

• Entry DOI: 10.2210/pdb1jln/pdb
• Descriptor: Protein Tyrosine Phosphatase, receptor type, R (2 entities in total)
• Functional Keywords: protein tyrosine phosphatase, ptp-sl, ptpbr7, erk2-map kinase regulation, hydrolase
• Biological source: Mus musculus (house mouse)
• Cellular location: Isoform Alpha: Cell membrane; Single-pass type I membrane protein. Isoform Beta: Cytoplasm. Isoform Gamma: Cytoplasm: Q62132
• Total number of polymer chains: 1
• Total formula weight: 33745.64

Authors

Szedlacsek, S.E.,Aricescu, A.R.,Fulga, T.A.,Renault, L.,Scheidig, A.J. (deposition date: 2001-07-16, release date: 2001-08-17, Last modification date: 2023-08-16)

Primary citation

Szedlacsek, S.E.,Aricescu, A.R.,Fulga, T.A.,Renault, L.,Scheidig, A.J.
Crystal structure of PTP-SL/PTPBR7 catalytic domain: implications for MAP kinase regulation.
J.Mol.Biol., 311:557-568, 2001

PubMed Abstract: 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.

PubMed: 11493009
DOI: 10.1006/jmbi.2001.4890

Experimental method

X-RAY DIFFRACTION (1.81 Å)