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2jmf

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Revision as of 06:36, 11 July 2018

Solution structure of the Su(dx) WW4- Notch PY peptide complex

Structural highlights

2jmf is a 2 chain structure with sequence from Drome. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1tk7
Gene:	Su dx (DROME), N (DROME)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SUDX_DROME] 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, probably by promoting Notch ubiquitination, endocytosis and degradation. Involved in wing growth and leg joint formation.^[1] ^[2] [NOTCH_DROME] Signaling protein, which regulates, with both positive and negative signals, the differentiation of at least central and peripheral nervous system and eye, wing disk, oogenesis, segmental appendages such as antennae and legs, and muscles, through lateral inhibition or induction. Functions as a receptor for membrane-bound ligands Delta and Serrate to regulate cell-fate determination. Upon ligand activation, and releasing from the cell membrane, the Notch intracellular domain (NICD) forms a transcriptional activator complex with Su(H) (Suppressor of hairless) and activates genes of the E(spl) complex. Essential for proper differentiation of ectoderm. Fringe (fng) acts in the Golgi to determine the type of O-linked fucose on the EGF modules in N, altering the ability of N to bind with Delta (Dl). O-fut1 also has a role in modulating the interaction. Rumi acts in the endoplasmic reticulum to glucosylate the EGF modules in N, this is required for correct folding and cleavage of N.^[3] ^[4]

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

WW domains target proline-tyrosine (PY) motifs and frequently function as tandem pairs. When studied in isolation, single WW domains are notably promiscuous and regulatory mechanisms are undoubtedly required to ensure selective interactions. Here, we show that the fourth WW domain (WW4) of Suppressor of Deltex, a modular Nedd4-like protein that down-regulates the Notch receptor, is the primary mediator of a direct interaction with a Notch-PY motif. A natural Trp to Phe substitution in WW4 reduces its affinity for general PY sequences and enhances selective interaction with the Notch-PY motif via compensatory specificity-determining interactions with PY-flanking residues. When WW4 is paired with WW3, domain-domain association, impeding proper folding, competes with Notch-PY binding to WW4. This novel mode of autoinhibition is relieved by binding of another ligand to WW3. Such cooperativity may facilitate the transient regulatory interactions observed in vivo between Su(dx) and Notch in the endocytic pathway. The highly conserved tandem arrangement of WW domains in Nedd4 proteins, and similar arrangements in more diverse proteins, suggests domain-domain communication may be integral to regulation of their associated cellular activities.

Specificity and autoregulation of Notch binding by tandem WW domains in suppressor of Deltex.,Jennings MD, Blankley RT, Baron M, Golovanov AP, Avis JM J Biol Chem. 2007 Sep 28;282(39):29032-42. Epub 2007 Jul 26. PMID:17656366^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mazaleyrat SL, Fostier M, Wilkin MB, Aslam H, Evans DA, Cornell M, Baron M. Down-regulation of Notch target gene expression by Suppressor of deltex. Dev Biol. 2003 Mar 15;255(2):363-72. PMID:12648496
↑ Wilkin MB, Carbery AM, Fostier M, Aslam H, Mazaleyrat SL, Higgs J, Myat A, Evans DA, Cornell M, Baron M. Regulation of notch endosomal sorting and signaling by Drosophila Nedd4 family proteins. Curr Biol. 2004 Dec 29;14(24):2237-44. PMID:15620650 doi:http://dx.doi.org/S0960982204008966
↑ Bruckner K, Perez L, Clausen H, Cohen S. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions. Nature. 2000 Jul 27;406(6794):411-5. PMID:10935637 doi:http://dx.doi.org/10.1038/35019075
↑ Acar M, Jafar-Nejad H, Takeuchi H, Rajan A, Ibrani D, Rana NA, Pan H, Haltiwanger RS, Bellen HJ. Rumi is a CAP10 domain glycosyltransferase that modifies Notch and is required for Notch signaling. Cell. 2008 Jan 25;132(2):247-58. doi: 10.1016/j.cell.2007.12.016. PMID:18243100 doi:http://dx.doi.org/10.1016/j.cell.2007.12.016
↑ Jennings MD, Blankley RT, Baron M, Golovanov AP, Avis JM. Specificity and autoregulation of Notch binding by tandem WW domains in suppressor of Deltex. J Biol Chem. 2007 Sep 28;282(39):29032-42. Epub 2007 Jul 26. PMID:17656366 doi:10.1074/jbc.M703453200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2jmf"

@@ Line 1: / Line 1: @@
 ==Solution structure of the Su(dx) WW4- Notch PY peptide complex==
 <StructureSection load='2jmf' size='340' side='right' caption='[[2jmf]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tk7|1tk7]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Su dx ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME]), N ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</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=2jmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jmf OCA], [http://pdbe.org/2jmf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jmf RCSB], [http://www.ebi.ac.uk/pdbsum/2jmf PDBsum]</span></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=2jmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jmf OCA], [http://pdbe.org/2jmf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jmf RCSB], [http://www.ebi.ac.uk/pdbsum/2jmf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2jmf ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 13: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jm/2jmf_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jm/2jmf_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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=2jmf ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">

2jmf

From Proteopedia

Revision as of 06:36, 11 July 2018

Solution structure of the Su(dx) WW4- Notch PY peptide complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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