4be8

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{{STRUCTURE_4be8| PDB=4be8 | SCENE= }}
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==NEDD4 HECT A889F structure==
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===NEDD4 HECT A889F structure===
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<StructureSection load='4be8' size='340' side='right' caption='[[4be8]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23644597}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4be8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BE8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BE8 FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bbn|4bbn]]</td></tr>
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<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=4be8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4be8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4be8 RCSB], [http://www.ebi.ac.uk/pdbsum/4be8 PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Homologous to E6-AP C terminus (HECT) E3 ligases recognize and directly catalyze ligation of ubiquitin (Ub) to their substrates. Molecular details of this process remain unknown. We report the first structure, to our knowledge, of a Ub-loaded E3, the human neural precursor cell-expressed developmentally downregulated protein 4 (Nedd4). The HECTNedd4~Ub transitory intermediate provides a structural basis for the proposed sequential addition mechanism. The donor Ub, transferred from the E2, is bound to the Nedd4 C lobe with its C-terminal tail locked in an extended conformation, primed for catalysis. We provide evidence that the Nedd4-family members are Lys63-specific enzymes whose catalysis is mediated by an essential C-terminal acidic residue.
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==Function==
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Structure of a ubiquitin-loaded HECT ligase reveals the molecular basis for catalytic priming.,Maspero E, Valentini E, Mari S, Cecatiello V, Soffientini P, Pasqualato S, Polo S Nat Struct Mol Biol. 2013 May 5. doi: 10.1038/nsmb.2566. PMID:23644597<ref>PMID:23644597</ref>
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[[http://www.uniprot.org/uniprot/NEDD4_HUMAN 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.<ref>PMID:17218260</ref> <ref>PMID:18562292</ref> <ref>PMID:20086093</ref> <ref>PMID:21765395</ref> <ref>PMID:21399620</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4be8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BE8 OCA].
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</div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:023644597</ref><references group="xtra"/><references/>
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*[[Ubiquitin protein ligase|Ubiquitin protein ligase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Cecatiello, V.]]
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[[Category: Cecatiello, V]]
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[[Category: Mari, S.]]
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[[Category: Mari, S]]
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[[Category: Maspero, E.]]
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[[Category: Maspero, E]]
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[[Category: Pasqualato, S.]]
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[[Category: Pasqualato, S]]
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[[Category: Polo, S.]]
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[[Category: Polo, S]]
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[[Category: Valentini, E.]]
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[[Category: Valentini, E]]
[[Category: Ligase]]
[[Category: Ligase]]

Revision as of 10:04, 21 December 2014

NEDD4 HECT A889F structure

4be8, resolution 3.00Å

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