6gbe

From Proteopedia

(Difference between revisions)

Current revision

Murine Protein Tyrosine Phosphatase PTPN13 PDZ3 Domain-PRK2 Peptide Complex

Structural highlights

6gbe is a 2 chain structure with sequence from Lk3 transgenic mice. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	Ptpn13, Ptp14 (LK3 transgenic mice)
Activity:	Protein-tyrosine-phosphatase, with EC number 3.1.3.48
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PTN13_MOUSE] Tyrosine phosphatase which regulates negatively FAS-induced apoptosis and NGFR-mediated pro-apoptotic signaling. [PKN2_HUMAN] PKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. Plays a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion, tumor cell invasion and transcription activation signaling processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and hence decreases CTTN ability to associate with filamentous actin. Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct RhoA target required for the regulation of the maturation of primordial junctions into apical junction formation in bronchial epithelial cells. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase activity that is required for establishment of skin cell-cell adhesion during keratinocytes differentiation. Regulates epithelial bladder cells speed and direction of movement during cell migration and tumor cell invasion. Inhibits Akt pro-survival-induced kinase activity. Mediates Rho protein-induced transcriptional activation via the c-fos serum response factor (SRF). Phosphorylates HCV NS5B leading to stimulation of HCV RNA replication.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10]

Publication Abstract from PubMed

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.

Molecular Basis of Class III Ligand Recognition by PDZ3 in Murine Protein Tyrosine Phosphatase PTPN13.,Kock G, Dicks M, Yip KT, Kohl B, Putz S, Heumann R, Erdmann KS, Stoll R J Mol Biol. 2018 Oct 19;430(21):4275-4292. doi: 10.1016/j.jmb.2018.08.023. Epub, 2018 Sep 3. PMID:30189200^[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Vincent S, Settleman J. The PRK2 kinase is a potential effector target of both Rho and Rac GTPases and regulates actin cytoskeletal organization. Mol Cell Biol. 1997 Apr;17(4):2247-56. PMID:9121475
↑ Balendran A, Casamayor A, Deak M, Paterson A, Gaffney P, Currie R, Downes CP, Alessi DR. PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2. Curr Biol. 1999 Apr 22;9(8):393-404. PMID:10226025
↑ Koh H, Lee KH, Kim D, Kim S, Kim JW, Chung J. Inhibition of Akt and its anti-apoptotic activities by tumor necrosis factor-induced protein kinase C-related kinase 2 (PRK2) cleavage. J Biol Chem. 2000 Nov 3;275(44):34451-8. PMID:10926925 doi:10.1074/jbc.M001753200
↑ Hodgkinson CP, Sale GJ. Regulation of both PDK1 and the phosphorylation of PKC-zeta and -delta by a C-terminal PRK2 fragment. Biochemistry. 2002 Jan 15;41(2):561-9. PMID:11781095
↑ Calautti E, Grossi M, Mammucari C, Aoyama Y, Pirro M, Ono Y, Li J, Dotto GP. Fyn tyrosine kinase is a downstream mediator of Rho/PRK2 function in keratinocyte cell-cell adhesion. J Cell Biol. 2002 Jan 7;156(1):137-48. Epub 2002 Jan 3. PMID:11777936 doi:http://dx.doi.org/10.1083/jcb.200105140
↑ Kim SJ, Kim JH, Kim YG, Lim HS, Oh JW. Protein kinase C-related kinase 2 regulates hepatitis C virus RNA polymerase function by phosphorylation. J Biol Chem. 2004 Nov 26;279(48):50031-41. Epub 2004 Sep 13. PMID:15364941 doi:http://dx.doi.org/10.1074/jbc.M408617200
↑ Schmidt A, Durgan J, Magalhaes A, Hall A. Rho GTPases regulate PRK2/PKN2 to control entry into mitosis and exit from cytokinesis. EMBO J. 2007 Mar 21;26(6):1624-36. Epub 2007 Mar 1. PMID:17332740 doi:http://dx.doi.org/10.1038/sj.emboj.7601637
↑ Harrison BC, Huynh K, Lundgaard GL, Helmke SM, Perryman MB, McKinsey TA. Protein kinase C-related kinase targets nuclear localization signals in a subset of class IIa histone deacetylases. FEBS Lett. 2010 Mar 19;584(6):1103-10. doi: 10.1016/j.febslet.2010.02.057. Epub, 2010 Feb 24. PMID:20188095 doi:http://dx.doi.org/10.1016/j.febslet.2010.02.057
↑ Wallace SW, Magalhaes A, Hall A. The Rho target PRK2 regulates apical junction formation in human bronchial epithelial cells. Mol Cell Biol. 2011 Jan;31(1):81-91. doi: 10.1128/MCB.01001-10. Epub 2010 Oct 25. PMID:20974804 doi:10.1128/MCB.01001-10
↑ Lachmann S, Jevons A, De Rycker M, Casamassima A, Radtke S, Collazos A, Parker PJ. Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration. PLoS One. 2011;6(7):e21732. doi: 10.1371/journal.pone.0021732. Epub 2011 Jul 6. PMID:21754995 doi:http://dx.doi.org/10.1371/journal.pone.0021732
↑ Kock G, Dicks M, Yip KT, Kohl B, Putz S, Heumann R, Erdmann KS, Stoll R. Molecular Basis of Class III Ligand Recognition by PDZ3 in Murine Protein Tyrosine Phosphatase PTPN13. J Mol Biol. 2018 Oct 19;430(21):4275-4292. doi: 10.1016/j.jmb.2018.08.023. Epub, 2018 Sep 3. PMID:30189200 doi:http://dx.doi.org/10.1016/j.jmb.2018.08.023

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6gbe"

@@ Line 1: / Line 1: @@
 ==Murine Protein Tyrosine Phosphatase PTPN13 PDZ3 Domain-PRK2 Peptide Complex==
-<StructureSection load='6gbe' size='340' side='right' caption='[[6gbe]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='6gbe' size='340' side='right'caption='[[6gbe]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6gbe]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GBE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GBE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6gbe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GBE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GBE FirstGlance]. <br>
-</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ptpn13, Ptp14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6gbe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gbe OCA], [http://pdbe.org/6gbe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gbe RCSB], [http://www.ebi.ac.uk/pdbsum/6gbe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gbe ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Protein-tyrosine-phosphatase]]
 [[Category: Kock, G]]

6gbe

From Proteopedia

Current revision

Murine Protein Tyrosine Phosphatase PTPN13 PDZ3 Domain-PRK2 Peptide Complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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