Sequence-specific 1H, 13C, and 15N assignment of the extended PDZ3 domain of the protein tyrosine phosphatase basophil-like PTP-BL

Kock, Gerd; Dicks, Markus; Heumann, Rolf; Erdmann, Kai S.; Stoll, Raphael

doi:10.1007/s12104-010-9242-9

Cited by 3 publications

(4 citation statements)

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“…Cloning, expression, and purification of the PDZ3 and PDZ2/PDZ3 tandem domain of murine PTPN13 has been published previously [28], [29]. The point mutant F31A of PDZ3 was generated through site-directed mutagenesis.…”

Section: Protein Expression and Purificationmentioning

confidence: 99%

“…The PRK2 resonances in complex with PDZ3 of PTPN13 were assigned based on 2D (transferred) 1 H-1 H NOESY as well as in a 2D 1 H-1 H double half filter (DHF) NOESY spectra [47]. Assignments have been published previously and have been deposited in the BioMagResBank (http://www.bmrb.wisc.edu) under accession numbers BMRB-16879 [28].…”

Section: Nmr Spectroscopymentioning

confidence: 99%

“…Based on the previously published NMR assignments, we now report here the structure in solution of the extended 12.7 kDa PDZ3 domain of PTPN13, which encompasses 119 residues, both in the apo-state and the PRK2-bound form [28].…”

Section: Introductionmentioning

confidence: 99%

“…Since PRK2 is the known physiological ligand of the PDZ3 domain of PTPN13, it is regarded as a class III representative. It is however also interesting to note, the PDZ3 domain of PTPN13 can also bind to class I ligands in vitro [1], [28].…”

Section: Introductionmentioning

confidence: 99%

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Molecular Basis of Class III Ligand Recognition by PDZ3 in Murine Protein Tyrosine Phosphatase PTPN13

Kock

Dicks

Yip

et al. 2018

Journal of Molecular Biology

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Protein tyrosine phosphatase PTPN13, also known as PTP-BL in mice, represents a large multi-domain non-transmembrane scaffolding protein that contains five consecutive PDZ domains. Here, we report the solution structures of the extended murine PTPN13 PDZ3 domain in its apo form and in complex with its physiological ligand, the carboxy-terminus of protein kinase C-related kinase-2 (PRK2), determined by multidimensional NMR spectroscopy. Both in its ligand-free state and when complexed to PRK2, PDZ3 of PTPN13 adopts the classical compact, globular D/E fold. PDZ3 of PTPN13 binds five carboxy-terminal amino acids of PRK2 via a groove located between the EB-strand and the DB-helix. The PRK2 peptide resides in the canonical PDZ3 binding cleft in an elongated manner and the amino acid side chains in position P0 and P-2, cysteine and aspartate, of the ligand face the groove between EB-strand and DB-helix, whereas the PRK2 side chains of tryptophan and alanine located in position P-1 and P-3 point away from the binding cleft. These structures are rare examples of selective class III ligand recognition by a PDZ domain and now provide a basis for the detailed structural investigation of the promiscuous interaction between the PDZ domains of PTPN13 and their ligands. They will also lead to a better understanding of the proposed scaffolding function of these domains in multi-protein complexes assembled by PTPN13 and could ultimately contribute to low molecular weight antagonists that might even act on the PRK2 signaling pathway to modulate rearrangements of the actin cytoskeleton.

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Section: Protein Expression and Purificationmentioning

confidence: 99%

Section: Nmr Spectroscopymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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