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4n7h

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Revision as of 04:21, 5 August 2016

Crystal Structure of the Complex of 3rd WW domain of Human Nedd4 and 1st PPXY Motif of ARRDC3

Structural highlights

4n7h is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4n7f
Gene:	KIAA0093, NEDD4, NEDD4-1, PIG53 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NEDD4_HUMAN] 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. Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. According to PubMed:18562292 the direct link between NEDD4 and PTEN regulation through polyubiquitination described in PubMed:17218260 is questionable. Involved in ubiquitination of ERBB4 intracellular domain E4ICD. Involved in the budding of many viruses. 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.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Following protracted stimulation, the beta2-adrenergic receptor (beta2AR) and many other G-protein-coupled receptors (GPCRs) are ubiquitinated and downregulated. Arrestin-Related Domain-Containing Protein-3 (ARRDC3) is an alpha-arrestin that recruits the ubiquitin ligase Nedd4 to the beta2AR. ARRDC3 contains two PPXY motifs that could potentially interact with any of the four WW domains of Nedd4. Here we dissect the interaction determinants. ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 muM for the third WW domain of Nedd4 binding to the first PPXY motif of Nedd4. Structures of the uncomplexed and PPXY1-bound WW3 domain were determined at 1.1 and 1.7 Angstrom resolution. The structures revealed conformational changes upon binding and the hydrogen bonding network in exquisite detail. Tight packing of ARRDC3 Val352, part of a 310 helix at the C-terminus of PPXY1, is important for high affinity binding to WW3. Although no single WW domain is strictly essential for the binding of Nedd4 and ARRDC3 expressed in HEK293 cells, high affinity binding of full-length ARRDC3 and Nedd4 is driven by the avid interaction of both PPXY motifs with either the WW2-WW3 or WW3-WW4 combinations, with Kd values as low as 300 nM.

Structural and Biochemical Basis for Ubiquitin Ligase Recruitment by Arrestin-Related Domain-Containing Protein-3 (ARRDC3).,Qi S, O'Hayre M, Gutkind JS, Hurley JH J Biol Chem. 2013 Dec 30. PMID:24379409^[6]

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

References

↑ Wang X, Trotman LC, Koppie T, Alimonti A, Chen Z, Gao Z, Wang J, Erdjument-Bromage H, Tempst P, Cordon-Cardo C, Pandolfi PP, Jiang X. NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell. 2007 Jan 12;128(1):129-39. PMID:17218260 doi:10.1016/j.cell.2006.11.039
↑ Fouladkou F, Landry T, Kawabe H, Neeb A, Lu C, Brose N, Stambolic V, Rotin D. The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization. Proc Natl Acad Sci U S A. 2008 Jun 24;105(25):8585-90. doi:, 10.1073/pnas.0803233105. Epub 2008 Jun 18. PMID:18562292 doi:10.1073/pnas.0803233105
↑ Lin Q, Wang J, Childress C, Sudol M, Carey DJ, Yang W. HECT E3 ubiquitin ligase Nedd4-1 ubiquitinates ACK and regulates epidermal growth factor (EGF)-induced degradation of EGF receptor and ACK. Mol Cell Biol. 2010 Mar;30(6):1541-54. doi: 10.1128/MCB.00013-10. Epub 2010 Jan, 19. PMID:20086093 doi:10.1128/MCB.00013-10
↑ Persaud A, Alberts P, Hayes M, Guettler S, Clarke I, Sicheri F, Dirks P, Ciruna B, Rotin D. Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function. EMBO J. 2011 Jul 15;30(16):3259-73. doi: 10.1038/emboj.2011.234. PMID:21765395 doi:10.1038/emboj.2011.234
↑ Maspero E, Mari S, Valentini E, Musacchio A, Fish A, Pasqualato S, Polo S. Structure of the HECT:ubiquitin complex and its role in ubiquitin chain elongation. EMBO Rep. 2011 Mar 11. PMID:21399620 doi:10.1038/embor.2011.21
↑ Qi S, O'Hayre M, Gutkind JS, Hurley JH. Structural and Biochemical Basis for Ubiquitin Ligase Recruitment by Arrestin-Related Domain-Containing Protein-3 (ARRDC3). J Biol Chem. 2013 Dec 30. PMID:24379409 doi:http://dx.doi.org/10.1074/jbc.M113.527473

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/4n7h"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the Complex of 3rd WW domain of Human Nedd4 and 1st PPXY Motif of ARRDC3==
 <StructureSection load='4n7h' size='340' side='right' caption='[[4n7h]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4n7f|4n7f]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KIAA0093, NEDD4, NEDD4-1, PIG53 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4n7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n7h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4n7h RCSB], [http://www.ebi.ac.uk/pdbsum/4n7h 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=4n7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n7h OCA], [http://pdbe.org/4n7h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4n7h RCSB], [http://www.ebi.ac.uk/pdbsum/4n7h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4n7h ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4n7h" style="background-color:#fffaf0;"></div>
 ==See Also==

4n7h

From Proteopedia

Revision as of 04:21, 5 August 2016

Crystal Structure of the Complex of 3rd WW domain of Human Nedd4 and 1st PPXY Motif of ARRDC3

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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