|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6j6u' size='340' side='right'caption='[[6j6u]], [[Resolution|resolution]] 3.32Å' scene=''> | | <StructureSection load='6j6u' size='340' side='right'caption='[[6j6u]], [[Resolution|resolution]] 3.32Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6j6u]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6J6U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6J6U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6j6u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6J6U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6J6U FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ptprz1, Ptprz, Ptpz ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.32Å</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'>[https://proteopedia.org/fgij/fg.htm?mol=6j6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j6u OCA], [https://pdbe.org/6j6u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6j6u RCSB], [https://www.ebi.ac.uk/pdbsum/6j6u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6j6u ProSAT]</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=6j6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j6u OCA], [http://pdbe.org/6j6u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6j6u RCSB], [http://www.ebi.ac.uk/pdbsum/6j6u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6j6u ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PTPRZ_RAT PTPRZ_RAT]] Protein tyrosine phosphatase that negatively regulates oligodendrocyte precursor proliferation in the embryonic spinal cord. Required for normal differentiation of the precursor cells into mature, fully myelinating oligodendrocytes. May play a role in protecting oligondendrocytes against apoptosis. May play a role in the establishment of contextual memory, probably via the dephosphorylation of proteins that are part of important signaling cascades (By similarity). Isoform 3 (phosphacan), previously designated 3F8 chondroitin sulfate proteoglycan or 3H1 keratan sulfate proteoglycan depending on the glycosylation status, is a soluble nervous tissue-specific proteoglycan. It is synthesized by glia and binds to neurons and to the neural cell adhesion molecules tenascin, N-CAM or NG-CAM but not to laminin and fibronectin. Phosphacan acts as a potent inhibitor of cell adhesion and neurite outgrowth. | + | [https://www.uniprot.org/uniprot/PTPRZ_RAT PTPRZ_RAT] Protein tyrosine phosphatase that negatively regulates oligodendrocyte precursor proliferation in the embryonic spinal cord. Required for normal differentiation of the precursor cells into mature, fully myelinating oligodendrocytes. May play a role in protecting oligondendrocytes against apoptosis. May play a role in the establishment of contextual memory, probably via the dephosphorylation of proteins that are part of important signaling cascades (By similarity). Isoform 3 (phosphacan), previously designated 3F8 chondroitin sulfate proteoglycan or 3H1 keratan sulfate proteoglycan depending on the glycosylation status, is a soluble nervous tissue-specific proteoglycan. It is synthesized by glia and binds to neurons and to the neural cell adhesion molecules tenascin, N-CAM or NG-CAM but not to laminin and fibronectin. Phosphacan acts as a potent inhibitor of cell adhesion and neurite outgrowth. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 19: |
Line 18: |
| | </div> | | </div> |
| | <div class="pdbe-citations 6j6u" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6j6u" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Protein-tyrosine-phosphatase]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Sugawara, H]] | + | [[Category: Sugawara H]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Protein tyrosine phosphatase]]
| + | |
| Structural highlights
Function
PTPRZ_RAT Protein tyrosine phosphatase that negatively regulates oligodendrocyte precursor proliferation in the embryonic spinal cord. Required for normal differentiation of the precursor cells into mature, fully myelinating oligodendrocytes. May play a role in protecting oligondendrocytes against apoptosis. May play a role in the establishment of contextual memory, probably via the dephosphorylation of proteins that are part of important signaling cascades (By similarity). Isoform 3 (phosphacan), previously designated 3F8 chondroitin sulfate proteoglycan or 3H1 keratan sulfate proteoglycan depending on the glycosylation status, is a soluble nervous tissue-specific proteoglycan. It is synthesized by glia and binds to neurons and to the neural cell adhesion molecules tenascin, N-CAM or NG-CAM but not to laminin and fibronectin. Phosphacan acts as a potent inhibitor of cell adhesion and neurite outgrowth.
Publication Abstract from PubMed
Protein tyrosine phosphatase receptor type Z (PTPRZ) has two receptor isoforms PTPRZ-A and -B, containing tandem intracellular PTP-D1 and -D2 domains, with only D1 being active. Pleiotrophin (PTN) binding to the extracellular PTPRZ region leads to inactivation of its PTPase activity, thereby facilitating oligodendrocyte precursor cell (OPC) differentiation and myelination in the central nervous system. However, the mechanisms responsible for PTN-induced PTPRZ inactivation remain unclear. We herein report that the crystal structure of the intracellular region of PTPRZ (PTPRZ-ICR) shows a "head-to-toe"-type dimer conformation, with D2 masking the catalytic site of D1. MS analyses revealed that PTPRZ-ICR proteins remain in monomer-dimer equilibrium in aqueous solution and that a substrate-derived inhibitory peptide or competitive inhibitor (SCB4380) specifically bind to the monomer form in a 1:1 ratio. A D2 deletion (DeltaD2) or dimer interface mutation (DDKK) disrupted dimer formation, but SCB4380 binding was maintained. Similar to wild-type PTPRZ-B, monomer-biased PTPRZ-B-DeltaD2 and PTPRZ-B-DDKK variants efficiently dephosphorylated p190RhoGAP at Tyr-1105 when co-expressed in BHK-21 cells. The catalytic activities of these variants were not suppressed by PTN treatment, but were inhibited by the cell-permeable PTPase inhibitor NAZ2329. Of note, the PTN treatment did not enhance OPC differentiation in primary cultured glial cells from DeltaD2 or PTPase-inactive PTPRZ-B (CS) mutant knock-in mice. Our results thus indicate that PTN-induced PTPRZ inactivation results from dimer formation of the intracellular tandem PTP domains in a head-to-toe configuration, which is physiologically relevant to the control of OPC differentiation in vivo.
A head-to-toe dimerization has physiological relevance for ligand-induced inactivation of protein tyrosine receptor type Z.,Fujikawa A, Sugawara H, Tanga N, Ishii K, Kuboyama K, Uchiyama S, Suzuki R, Noda M J Biol Chem. 2019 Aug 15. pii: RA119.007878. doi: 10.1074/jbc.RA119.007878. PMID:31416834[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fujikawa A, Sugawara H, Tanga N, Ishii K, Kuboyama K, Uchiyama S, Suzuki R, Noda M. A head-to-toe dimerization has physiological relevance for ligand-induced inactivation of protein tyrosine receptor type Z. J Biol Chem. 2019 Aug 15. pii: RA119.007878. doi: 10.1074/jbc.RA119.007878. PMID:31416834 doi:http://dx.doi.org/10.1074/jbc.RA119.007878
|
