2n8t

From Proteopedia

(Difference between revisions)

Revision as of 09:45, 26 December 2018

Solution Structure of the rNedd4 WW2 Domain-Cx43CT Peptide Complex by NMR

Structural highlights

2n8t is a 2 chain structure with sequence from Buffalo rat. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Related:	2n8s, 2n8u
Gene:	Nedd4, Nedd4a (Buffalo rat)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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] [CXA1_RAT] Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. Negative regulator of bladder functional capacity: acts by enhancing intercellular electrical and chemical transmission, thus sensitizing bladder muscles to cholinergic neural stimuli and causing them to contract (By similarity).

Publication Abstract from PubMed

Nedd4 was the first ubiquitin protein ligase identified to interact with Cx43 and its suppressed expression results in accumulation of gap junction plaques at the plasma membrane. Nedd4-mediated ubiquitination of Cx43 is required to recruit Eps15 and target Cx43 to the endocytic pathway. While the Cx43 residues that undergo ubiquitination are still unknown, in this study we address other unresolved questions pertaining to the molecular mechanisms mediating the direct interaction between Nedd4 (WW1-3 domains) and Cx43 (carboxyl terminus, CT). All three WW domains display a similar three antiparallel beta-strand structure and interact with the same Cx43CT 283PPxY286 sequence. While Y286 is essential for the interaction, MAPK phosphorylation of the preceding serine residues (pS282 and pS279) increases the binding affinity by two-fold for the WW domains (WW2>WW3>>WW1). The structure of the WW2/Cx43CTpS282,pS279 complex reveals that coordination of pS282 with the end of beta strand 3 enables pS279 to interact with the back face of beta strand 3 (Y286 is on the front face) and loop 2, forming a horseshoe-shaped structure. The close sequence identity of WW2 with WW1 and WW3 residues that interact with the Cx43CT PPxY motif and pS282/pS279 strongly suggest that the significantly lower binding affinity of WW1 is the result of a more rigid structure. This study presents the first structure illustrating how phosphorylation of the Cx43CT domain helps mediate the interaction with a molecular partner involved in gap junction regulation.

Structural Studies of the Nedd4 WW Domains and their Selectivity for the Cx43 Carboxyl-terminus.,Spagnol G, Kieken F, Kopanic JL, Li H, Zach S, Stauch KL, Grosely R, Sorgen PL J Biol Chem. 2016 Feb 3. pii: jbc.M115.701417. PMID:26841867^[2]

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

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
↑ Spagnol G, Kieken F, Kopanic JL, Li H, Zach S, Stauch KL, Grosely R, Sorgen PL. Structural Studies of the Nedd4 WW Domains and their Selectivity for the Cx43 Carboxyl-terminus. J Biol Chem. 2016 Feb 3. pii: jbc.M115.701417. PMID:26841867 doi:http://dx.doi.org/10.1074/jbc.M115.701417

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2n8t"

@@ Line 3: / Line 3: @@
 <StructureSection load='2n8t' size='340' side='right' caption='[[2n8t]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2n8t]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N8T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N8T FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2n8t]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N8T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N8T FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2n8s|2n8s]], [[2n8u|2n8u]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nedd4, Nedd4a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=2n8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n8t OCA], [http://pdbe.org/2n8t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n8t RCSB], [http://www.ebi.ac.uk/pdbsum/2n8t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2n8t ProSAT]</span></td></tr>
 </table>
@@ Line 26: / Line 27: @@
 __TOC__
 </StructureSection>
+[[Category: Buffalo rat]]
 [[Category: Kieken, F]]
 [[Category: Sorgen, P L]]

2n8t

From Proteopedia

Revision as of 09:45, 26 December 2018

Solution Structure of the rNedd4 WW2 Domain-Cx43CT Peptide Complex by NMR

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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