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| | ==SOLUTION STRUCTURE OF THE RNEDD4 WWIII DOMAIN-RENAL BP2 PEPTIDE COMPLEX== | | ==SOLUTION STRUCTURE OF THE RNEDD4 WWIII DOMAIN-RENAL BP2 PEPTIDE COMPLEX== |
| - | <StructureSection load='1i5h' size='340' side='right'caption='[[1i5h]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | + | <StructureSection load='1i5h' size='340' side='right'caption='[[1i5h]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1i5h]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1I5H FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1i5h]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1I5H FirstGlance]. <br> |
| - | </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=1i5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i5h OCA], [https://pdbe.org/1i5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1i5h RCSB], [https://www.ebi.ac.uk/pdbsum/1i5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1i5h ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1i5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i5h OCA], [https://pdbe.org/1i5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1i5h RCSB], [https://www.ebi.ac.uk/pdbsum/1i5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1i5h ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/NEDD4_RAT NEDD4_RAT]] 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. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Is involved in ubiquitination of ERBB4 intracellular domain E4ICD. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2 (By similarity).<ref>PMID:20159449</ref> [[https://www.uniprot.org/uniprot/SCNNB_RAT SCNNB_RAT]] Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception.
| + | [https://www.uniprot.org/uniprot/NEDD4_RAT NEDD4_RAT] 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. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Is involved in ubiquitination of ERBB4 intracellular domain E4ICD. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2 (By similarity).<ref>PMID:20159449</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Forman-Kay, J D]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Kanelis, V]] | + | [[Category: Forman-Kay JD]] |
| - | [[Category: Rotin, D]]
| + | [[Category: Kanelis V]] |
| - | [[Category: Enac]]
| + | [[Category: Rotin D]] |
| - | [[Category: Liddle syndrome]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Nedd4]]
| + | |
| - | [[Category: Proline-rich]]
| + | |
| - | [[Category: Py motif]] | + | |
| - | [[Category: Ww domain]] | + | |
| Structural highlights
Function
NEDD4_RAT 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. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Is involved in ubiquitination of ERBB4 intracellular domain E4ICD. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2 (By similarity).[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Nedd4 is a ubiquitin protein ligase composed of a C2 domain, three (or four) WW domains and a ubiquitin ligase Hect domain. Nedd4 was demonstrated to bind the epithelial sodium channel (alphabetagammaENaC), by association of its WW domains with PY motifs (XPPXY) present in each ENaC subunit, and to regulate the cell surface stability of the channel. The PY motif of betaENaC is deleted or mutated in Liddle syndrome, a hereditary form of hypertension caused by elevated ENaC activity. Here we report the solution structure of the third WW domain of Nedd4 complexed to the PY motif-containing region of betaENaC (TLPIPGTPPPNYDSL, referred to as betaP2). A polyproline type II helical conformation is adopted by the PPPN sequence. Unexpectedly, the C-terminal sequence YDSL forms a helical turn and both the tyrosine and the C-terminal leucine contact the WW domain. This is unlike other proline-rich peptides complexed to WW domains, which bind in an extended conformation and lack molecular interactions with residues C-terminal to the tyrosine or the structurally equivalent residue in non-PY motif WW domain targets. The Nedd4 WW domain-ENaC betaP2 peptide structure expands our understanding of the mechanisms involved in WW domain-ligand recognition and the molecular basis of Liddle syndrome.
Solution structure of a Nedd4 WW domain-ENaC peptide complex.,Kanelis V, Rotin D, Forman-Kay JD Nat Struct Biol. 2001 May;8(5):407-12. PMID:11323714[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kawabe H, Neeb A, Dimova K, Young SM Jr, Takeda M, Katsurabayashi S, Mitkovski M, Malakhova OA, Zhang DE, Umikawa M, Kariya K, Goebbels S, Nave KA, Rosenmund C, Jahn O, Rhee J, Brose N. Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. Neuron. 2010 Feb 11;65(3):358-72. doi: 10.1016/j.neuron.2010.01.007. PMID:20159449 doi:10.1016/j.neuron.2010.01.007
- ↑ Kanelis V, Rotin D, Forman-Kay JD. Solution structure of a Nedd4 WW domain-ENaC peptide complex. Nat Struct Biol. 2001 May;8(5):407-12. PMID:11323714 doi:10.1038/87562
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