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< | ==Solution Structure of the dNedd4 WW3* Domain- Comm LPSY Peptide Complex== | ||
<StructureSection load='2ez5' size='340' side='right'caption='[[2ez5]]' scene=''> | |||
You may | == Structural highlights == | ||
<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> | |||
- | </table> | ||
== 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> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ez/2ez5_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ez5 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:16531238</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2ez5" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
< | |||
[[Category: Drosophila melanogaster]] | [[Category: Drosophila melanogaster]] | ||
[[Category: Bruce | [[Category: Large Structures]] | ||
[[Category: Forman-Kay | [[Category: Bruce MC]] | ||
[[Category: Kanelis | [[Category: Forman-Kay JD]] | ||
[[Category: Rotin | [[Category: Kanelis V]] | ||
[[Category: Skrynnikov | [[Category: Rotin D]] | ||
[[Category: Skrynnikov NR]] | |||
Latest revision as of 12:58, 21 December 2022
Solution Structure of the dNedd4 WW3* Domain- Comm LPSY Peptide ComplexSolution Structure of the dNedd4 WW3* Domain- Comm LPSY Peptide Complex
Structural highlights
FunctionNEDD4_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 PubMedInteractions 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 AlsoReferences
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