4k7d: Difference between revisions

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{{STRUCTURE_4k7d|  PDB=4k7d  |  SCENE=  }}
==Crystal Structure of Parkin C-terminal RING domains==
===Crystal Structure of Parkin C-terminal RING domains===
<StructureSection load='4k7d' size='340' side='right' caption='[[4k7d]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
{{ABSTRACT_PUBMED_23661642}}
== Structural highlights ==
<table><tr><td colspan='2'>[[4k7d]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K7D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K7D FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Park2, Prkn ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</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=4k7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k7d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k7d RCSB], [http://www.ebi.ac.uk/pdbsum/4k7d PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mutations in the Parkin gene are responsible for an autosomal recessive form of Parkinson's disease. The parkin protein is a RING-In-Between-RING (RBR) E3 ubiquitin ligase, which exhibits low basal activity. Here, we describe the crystal structure of full-length parkin. The structure shows parkin in an auto-inhibited state and provides insight into how it is activated. RING0 occludes the ubiquitin acceptor site Cys431 in RING2, whereas a repressor element of parkin (REP) binds RING1 and blocks its E2-binding site. Mutations that disrupted these inhibitory interactions activated parkin both in vitro and in cells. Parkin is neuroprotective and these findings may provide a structural and mechanistic framework for enhancing parkin activity.


==Function==
Structure of Parkin Reveals Mechanisms for Ubiquitin Ligase Activation.,Trempe JF, Sauve V, Grenier K, Seirafi M, Tang MY, Menade M, Al-Abdul-Wahid S, Krett J, Wong K, Kozlov G, Nagar B, Fon EA, Gehring K Science. 2013 May 9. PMID:23661642<ref>PMID:23661642</ref>
[[http://www.uniprot.org/uniprot/PRKN2_RAT PRKN2_RAT]] Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, STUB1, a 22 kDa O-linked glycosylated isoform of SNCAIP, SEPT5, ZNF746 and AIMP2. Mediates monoubiquitination as well as 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation. Mediates 'Lys-63'-linked polyubiquitination of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. Promotes the autophagic degradation of dysfunctional depolarized mitochondria. Mediates 'Lys-48'-linked polyubiquitination of ZNF746, followed by degradation of ZNF746 by the proteasome; possibly playing a role in role in regulation of neuron death. Limits the production of reactive oxygen species (ROS). Loss of this ubiquitin ligase activity appears to be the mechanism underlying pathogenesis of PARK2. May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity. May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. Regulates cyclin-E during neuronal apoptosis. May represent a tumor suppressor gene (By similarity).  


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[4k7d]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K7D OCA].
</div>


==Reference==
==See Also==
<ref group="xtra">PMID:023661642</ref><references group="xtra"/><references/>
*[[Ubiquitin protein ligase|Ubiquitin protein ligase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Gehring, K.]]
[[Category: Gehring, K]]
[[Category: Menade, M.]]
[[Category: Menade, M]]
[[Category: Sauve, V.]]
[[Category: Sauve, V]]
[[Category: Trempe, J F.]]
[[Category: Trempe, J F]]
[[Category: E3 ubiquitin protein ligase]]
[[Category: E3 ubiquitin protein ligase]]
[[Category: Ligase]]
[[Category: Ligase]]
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