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| | ==Solution Structure of the dNedd4 WW3* Domain- Comm LPSY Peptide Complex== | | ==Solution Structure of the dNedd4 WW3* Domain- Comm LPSY Peptide Complex== |
| - | <StructureSection load='2ez5' size='340' side='right'caption='[[2ez5]], [[NMR_Ensembles_of_Models | 30 NMR models]]' scene=''> | + | <StructureSection load='2ez5' size='340' side='right'caption='[[2ez5]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ez5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drome Drome]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EZ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2EZ5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ez5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EZ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2EZ5 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=2ez5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ez5 OCA], [https://pdbe.org/2ez5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ez5 RCSB], [https://www.ebi.ac.uk/pdbsum/2ez5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ez5 ProSAT]</span></td></tr> | | </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=2ez5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ez5 OCA], [https://pdbe.org/2ez5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ez5 RCSB], [https://www.ebi.ac.uk/pdbsum/2ez5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ez5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/NEDD4_DROME NEDD4_DROME]] Essential 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. Down-regulates Notch/N signaling pathway by promoting Notch ubiquitination, endocytosis and degradation.<ref>PMID:12165468</ref> <ref>PMID:15620649</ref> <ref>PMID:15657595</ref> [[https://www.uniprot.org/uniprot/COMM_DROME COMM_DROME]] Controls axon guidance across the CNS midline by preventing the delivery of Robo to the growth cone.<ref>PMID:12165468</ref> <ref>PMID:15657595</ref>
| + | [https://www.uniprot.org/uniprot/NEDD4_DROME NEDD4_DROME] Essential 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. Down-regulates Notch/N signaling pathway by promoting Notch ubiquitination, endocytosis and degradation.<ref>PMID:12165468</ref> <ref>PMID:15620649</ref> <ref>PMID:15657595</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Drome]] | + | [[Category: Drosophila melanogaster]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bruce, M C]] | + | [[Category: Bruce MC]] |
| - | [[Category: Forman-Kay, J D]] | + | [[Category: Forman-Kay JD]] |
| - | [[Category: Kanelis, V]] | + | [[Category: Kanelis V]] |
| - | [[Category: Rotin, D]] | + | [[Category: Rotin D]] |
| - | [[Category: Skrynnikov, N R]] | + | [[Category: Skrynnikov NR]] |
| - | [[Category: Binding affinity]]
| + | |
| - | [[Category: Commissureless]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Nedd4]]
| + | |
| - | [[Category: Py motif]]
| + | |
| - | [[Category: Signalling protein]]
| + | |
| - | [[Category: Ww domain]]
| + | |
| Structural highlights
Function
NEDD4_DROME Essential 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. Down-regulates Notch/N signaling pathway by promoting Notch ubiquitination, endocytosis and degradation.[1] [2] [3]
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
Interactions between the WW domains of Drosophila Nedd4 (dNedd4) and Commissureless (Comm) PY motifs promote axon crossing at the CNS midline and muscle synaptogenesis. Here we report the solution structure of the dNedd4 WW3* domain complexed to the second PY motif (227'TGLPSYDEALH237') of Comm. Unexpectedly, there are interactions between WW3* and ligand residues both N- and C-terminal to the PY motif. Residues Y232'-L236' form a helical turn, following the PPII helical PY motif. Mutagenesis and binding studies confirm the importance of these extensive contacts, not simultaneously observed in other WW domain complexes, and identify a variable loop in WW3* responsible for its high-affinity interaction. These studies expand our general understanding of the molecular determinants involved in WW domain-ligand recognition. In addition, they provide insights into the specific regulation of dNedd4-mediated ubiquitination of Comm and subsequent internalization of Comm or the Comm/Roundabout complex, critical for CNS and muscle development.
Structural determinants for high-affinity binding in a Nedd4 WW3* domain-Comm PY motif complex.,Kanelis V, Bruce MC, Skrynnikov NR, Rotin D, Forman-Kay JD Structure. 2006 Mar;14(3):543-53. PMID:16531238[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Myat A, Henry P, McCabe V, Flintoft L, Rotin D, Tear G. Drosophila Nedd4, a ubiquitin ligase, is recruited by Commissureless to control cell surface levels of the roundabout receptor. Neuron. 2002 Aug 1;35(3):447-59. PMID:12165468
- ↑ Sakata T, Sakaguchi H, Tsuda L, Higashitani A, Aigaki T, Matsuno K, Hayashi S. Drosophila Nedd4 regulates endocytosis of notch and suppresses its ligand-independent activation. Curr Biol. 2004 Dec 29;14(24):2228-36. PMID:15620649 doi:http://dx.doi.org/10.1016/j.cub.2004.12.028
- ↑ Keleman K, Ribeiro C, Dickson BJ. Comm function in commissural axon guidance: cell-autonomous sorting of Robo in vivo. Nat Neurosci. 2005 Feb;8(2):156-63. Epub 2005 Jan 16. PMID:15657595 doi:http://dx.doi.org/10.1038/nn1388
- ↑ Kanelis V, Bruce MC, Skrynnikov NR, Rotin D, Forman-Kay JD. Structural determinants for high-affinity binding in a Nedd4 WW3* domain-Comm PY motif complex. Structure. 2006 Mar;14(3):543-53. PMID:16531238 doi:10.1016/j.str.2005.11.018
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