View source for 6opc


==Cdc48 Hexamer in a complex with substrate and Shp1(Ubx Domain)==
<SX load='6opc' size='340' side='right' viewer='molstar' caption='[[6opc]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6opc]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OPC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OPC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6opc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6opc OCA], [https://pdbe.org/6opc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6opc RCSB], [https://www.ebi.ac.uk/pdbsum/6opc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6opc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CDC48_YEAST CDC48_YEAST] ATP-dependent chaperone which probably uses the energy provided by ATP hydrolysis to generate mechanical force to unfold substrate proteins, disassemble protein complexes, and disaggregate protein aggregates (PubMed:21454554). By recruiting and promoting the degradation of ubiquitinated proteins, plays a role in the ubiquitin fusion degradation (UFD) pathway (PubMed:16428438). Has a role in the endoplasmic reticulum-associated degradation (ERAD) pathway which mediates the cytoplasmic elimination of misfolded proteins exported from the ER (PubMed:11813000, PubMed:11740563, PubMed:11847109, PubMed:21148305). Required for the proteasome-dependent processing/activation of MGA2 and SPT23 transcription factors leading to the subsequent expression of OLE1 (PubMed:11847109, PubMed:11733065). Has an additional role in the turnover of OLE1 where it targets ubiquitinated OLE1 and other proteins to the ERAD (PubMed:11847109). Regulates ubiquitin-mediated mitochondria protein degradation (PubMed:21070972, PubMed:27044889). Involved in spindle disassembly probably by promoting the degradation of spindle assembly factors ASE1 and CDC5 at the end of mitosis (PubMed:14636562). Component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation (PubMed:23178123, PubMed:24261871). CDC48 may provide the mechanical force that dislodges the polyubiquitinated nascent peptides from the exit channel (PubMed:23178123, PubMed:24261871). Required for ribophagy, a process which relocalizes ribosomal particles into the vacuole for degradation in response to starvation (PubMed:20508643).<ref>PMID:11733065</ref> <ref>PMID:11740563</ref> <ref>PMID:11813000</ref> <ref>PMID:11847109</ref> <ref>PMID:14636562</ref> <ref>PMID:16428438</ref> <ref>PMID:20508643</ref> <ref>PMID:21070972</ref> <ref>PMID:21148305</ref> <ref>PMID:21454554</ref> <ref>PMID:23178123</ref> <ref>PMID:24261871</ref> <ref>PMID:27044889</ref> 
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== Publication Abstract from PubMed ==
The cellular machine Cdc48 functions in multiple biological pathways by segregating its protein substrates from a variety of stable environments such as organelles or multi-subunit complexes. Despite extensive studies, the mechanism of Cdc48 has remained obscure, and its reported structures are inconsistent with models of substrate translocation proposed for other AAA+ ATPases. Here, we report a 3.7 A resolution structure of Cdc48 in complex with an adaptor protein and a native substrate. Cdc48 engages substrate by adopting a helical configuration of substrate-binding residues that extends through the central pore of both of the ATPase rings. These findings indicate a unified hand-over-hand mechanism of protein translocation by Cdc48 and other AAA+ ATPases.

Structure of the Cdc48 segregase in the act of unfolding an authentic substrate.,Cooney I, Han H, Stewart MG, Carson RH, Hansen DT, Iwasa JH, Price JC, Hill CP, Shen PS Science. 2019 Jun 27. pii: science.aax0486. doi: 10.1126/science.aax0486. PMID:31249134<ref>PMID:31249134</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6opc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</SX>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Carson RH]]
[[Category: Cooney I]]
[[Category: Han H]]
[[Category: Hansen D]]
[[Category: Hill CP]]
[[Category: Price JC]]
[[Category: Shen PS]]
[[Category: Stewart M]]