3nfl
From Proteopedia
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| - | [[ | + | ==Crystal structure of the PTPN4 PDZ domain complexed with the C-terminus of the GluN2A NMDA receptor subunit== |
| + | <StructureSection load='3nfl' size='340' side='right' caption='[[3nfl]], [[Resolution|resolution]] 1.91Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3nfl]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NFL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NFL FirstGlance]. <br> | ||
| + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vph|2vph]], [[2cs5|2cs5]], [[3nfk|3nfk]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPN4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3nfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nfl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nfl RCSB], [http://www.ebi.ac.uk/pdbsum/3nfl PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/NMDE1_HUMAN NMDE1_HUMAN]] Landau-Kleffner syndrome;Early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation;Continuous spikes and waves during sleep;Rolandic epilepsy;Rolandic epilepsy - speech dyspraxia. The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving GRIN2A has been found in a family with epilepsy and neurodevelopmental defects. Translocation t(16;17)(p13.2;q11.2). GRIN2A somatic mutations have been frequently found in cutaneous malignant melanoma, suggesting that the glutamate signaling pathway may play a role in the pathogenesis of melanoma.<ref>PMID:21499247</ref> <ref>PMID:24455489</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/PTN4_HUMAN PTN4_HUMAN]] May act at junctions between the membrane and the cytoskeleton. [[http://www.uniprot.org/uniprot/NMDE1_HUMAN NMDE1_HUMAN]] NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Activation requires binding of agonist to both types of subunits. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | PTPN4, a human tyrosine phosphatase, protects cells against apoptosis. This protection could be abrogated by targeting the PDZ domain of this phosphatase with a peptide mimicking the C-terminal sequence of the G protein of an attenuated rabies virus strain. Here, we demonstrate that glioblastoma death is triggered upon intracellular delivery of peptides, either from viral origin or from known endogenous ligands of PTPN4-PDZ, such as the C terminus sequence of the glutamate receptor subunit GluN2A. The killing efficiency of peptides closely reflects their affinities for the PTPN4-PDZ. The crystal structures of two PTPN4-PDZ/peptide complexes allow us to pinpoint the main structural determinants of binding and to synthesize a peptide of high affinity for PTPN4-PDZ enhancing markedly its cell death capacity. These results allow us to propose a potential mechanism for the efficiency of peptides and provide a target and a robust framework for the design of new pro-death compounds. | ||
| - | + | Peptides targeting the PDZ domain of PTPN4 are efficient inducers of glioblastoma cell death.,Babault N, Cordier F, Lafage M, Cockburn J, Haouz A, Prehaud C, Rey FA, Delepierre M, Buc H, Lafon M, Wolff N Structure. 2011 Oct 12;19(10):1518-24. PMID:22000519<ref>PMID:22000519</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Tyrosine phosphatase|Tyrosine phosphatase]] | *[[Tyrosine phosphatase|Tyrosine phosphatase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Babault, N | + | [[Category: Babault, N]] |
| - | [[Category: Buc, H | + | [[Category: Buc, H]] |
| - | [[Category: Cockburn, J | + | [[Category: Cockburn, J]] |
| - | [[Category: Cordier, F | + | [[Category: Cordier, F]] |
| - | [[Category: Delepierre, M | + | [[Category: Delepierre, M]] |
| - | [[Category: Haouz, A | + | [[Category: Haouz, A]] |
| - | [[Category: Lafage, M | + | [[Category: Lafage, M]] |
| - | [[Category: Lafon, M | + | [[Category: Lafon, M]] |
| - | [[Category: Rey, F A | + | [[Category: Rey, F A]] |
| - | [[Category: Wolff, N | + | [[Category: Wolff, N]] |
[[Category: Pdz-pdz-binding site complex]] | [[Category: Pdz-pdz-binding site complex]] | ||
[[Category: Protein binding]] | [[Category: Protein binding]] | ||
Revision as of 11:24, 9 December 2014
Crystal structure of the PTPN4 PDZ domain complexed with the C-terminus of the GluN2A NMDA receptor subunit
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