2mpt
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 2mpt is ON HOLD Authors: Escobedo, A., Macias, M.J., Gomes, T., Aragon, E., Martin-Malpartida, P., Ruiz, L. Description: WW3 domain of Nedd4L in co...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==WW3 domain of Nedd4L in complex with its HECT domain PY motif== | |
| + | <StructureSection load='2mpt' size='340' side='right'caption='[[2mpt]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2mpt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MPT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MPT FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></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=2mpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mpt OCA], [https://pdbe.org/2mpt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mpt RCSB], [https://www.ebi.ac.uk/pdbsum/2mpt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mpt ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/NED4L_HUMAN NED4L_HUMAN] E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, EAAT1 or CLC5. Promotes ubiquitination and degradation of SGK1 and TNK2.<ref>PMID:12911626</ref> <ref>PMID:15217910</ref> <ref>PMID:15489223</ref> <ref>PMID:15040001</ref> <ref>PMID:15496141</ref> <ref>PMID:15576372</ref> <ref>PMID:19144635</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | We investigated the mechanisms of activation and degradation of the E3 ubiquitin ligase Nedd4L combining the available biochemical information with complementary biophysical techniques. Using nuclear magnetic resonance spectroscopy, we identified that the C2 domain binds Ca(2+) and inositol 1,4,5-trisphosphate (IP3) using the same interface that is used to interact with the HECT domain. Thus, we propose that the transition from the closed to the active form is regulated by a competition of IP3 and Ca(2+) with the HECT domain for binding to the C2 domain. We performed relaxation experiments and molecular dynamic simulations to determine the flexibility of the HECT structure and observed that its conserved PY motif can become solvent-exposed when the unfolding process is initiated. The structure of the WW3 domain bound to the HECT-PY site reveals the details of this interaction, suggesting a possible auto-ubquitination mechanism using two molecules, a partially unfolded one and a fully functional Nedd4L counterpart. | ||
| - | + | Structural Basis of the Activation and Degradation Mechanisms of the E3 Ubiquitin Ligase Nedd4L.,Escobedo A, Gomes T, Aragon E, Martin-Malpartida P, Ruiz L, Macias MJ Structure. 2014 Oct 7;22(10):1446-57. doi: 10.1016/j.str.2014.08.016. PMID:25295397<ref>PMID:25295397</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 2mpt" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Aragon E]] | ||
| + | [[Category: Escobedo A]] | ||
| + | [[Category: Gomes T]] | ||
| + | [[Category: Macias MJ]] | ||
| + | [[Category: Martin-Malpartida P]] | ||
| + | [[Category: Ruiz L]] | ||
Current revision
WW3 domain of Nedd4L in complex with its HECT domain PY motif
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