View source for 6qs8


==ClpB (DWB and K476C mutant) bound to casein in presence of ATPgammaS - state KC-2B==
<SX load='6qs8' size='340' side='right' viewer='molstar' caption='[[6qs8]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qs8]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895] and [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QS8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QS8 FirstGlance]. <br>
</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=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">clpB, htpM, b2592, JW2573 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6qs8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qs8 OCA], [http://pdbe.org/6qs8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qs8 RCSB], [http://www.ebi.ac.uk/pdbsum/6qs8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qs8 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/CLPB_ECOLI CLPB_ECOLI]] Part of a stress-induced multi-chaperone system, it is involved in the recovery of the cell from heat-induced damage, in cooperation with DnaK, DnaJ and GrpE. Acts before DnaK, in the processing of protein aggregates. Protein binding stimulates the ATPase activity; ATP hydrolysis unfolds the denatured protein aggregates, which probably helps expose new hydrophobic binding sites on the surface of ClpB-bound aggregates, contributing to the solubilization and refolding of denatured protein aggregates by DnaK.<ref>PMID:10982797</ref> <ref>PMID:12624113</ref> <ref>PMID:14640692</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
AAA+ proteins form asymmetric hexameric rings that hydrolyze ATP and thread substrate proteins through a central channel via mobile substrate-binding pore loops. Understanding how ATPase and threading activities are regulated and intertwined is key to understanding the AAA+ protein mechanism. We studied the disaggregase ClpB, which contains tandem ATPase domains (AAA1, AAA2) and shifts between low and high ATPase and threading activities. Coiled-coil M-domains repress ClpB activity by encircling the AAA1 ring. Here, we determine the mechanism of ClpB activation by comparing ATPase mechanisms and cryo-EM structures of ClpB wild-type and a constitutively active ClpB M-domain mutant. We show that ClpB activation reduces ATPase cooperativity and induces a sequential mode of ATP hydrolysis in the AAA2 ring, the main ATPase motor. AAA1 and AAA2 rings do not work synchronously but in alternating cycles. This ensures high grip, enabling substrate threading via a processive, rope-climbing mechanism.

Two-Step Activation Mechanism of the ClpB Disaggregase for Sequential Substrate Threading by the Main ATPase Motor.,Deville C, Franke K, Mogk A, Bukau B, Saibil HR Cell Rep. 2019 Jun 18;27(12):3433-3446.e4. doi: 10.1016/j.celrep.2019.05.075. PMID:31216466<ref>PMID:31216466</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6qs8" style="background-color:#fffaf0;"></div>

==See Also==
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
== References ==
<references/>
__TOC__
</SX>
[[Category: Bacillus coli migula 1895]]
[[Category: Bos taurus]]
[[Category: Large Structures]]
[[Category: Deville, C]]
[[Category: Saibil, H R]]
[[Category: Aaa]]
[[Category: Chaperone]]
[[Category: Disaggregase]]
[[Category: Proteostasis]]