7qby

<StructureSection load='7qby' size='340' side='right'caption='[[7qby]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>

<table><tr><td colspan='2'>[[7qby]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QBY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QBY FirstGlance]. <br>

</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6u3s|6u3s]], [[6u3r|6u3r]], [[7jsq|7jsq]]</div></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=7qby FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qby OCA], [https://pdbe.org/7qby PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qby RCSB], [https://www.ebi.ac.uk/pdbsum/7qby PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qby ProSAT]</span></td></tr>

== Disease ==

[[https://www.uniprot.org/uniprot/DNJB6_HUMAN DNJB6_HUMAN]] Autosomal dominant limb-girdle muscular dystrophy type 1D. The disease is caused by mutations affecting the gene represented in this entry. There is evidence that LGMDD1 is caused by dysfunction of isoform B (PubMed:22366786).<ref>PMID:22366786</ref>

== Function ==

[[https://www.uniprot.org/uniprot/DNJB6_HUMAN DNJB6_HUMAN]] Plays an indispensable role in the organization of KRT8/KRT18 filaments. Acts as an endogenous molecular chaperone for neuronal proteins including huntingtin. Suppresses aggregation and toxicity of polyglutamine-containing, aggregation-prone proteins. Isoform B but not isoform A inhibits huntingtin aggregation. Has a stimulatory effect on the ATPase activity of HSP70 in a dose-dependent and time-dependent manner and hence acts as a co-chaperone of HSP70. Also reduces cellular toxicity and caspase-3 activity.<ref>PMID:10954706</ref> <ref>PMID:11896048</ref> <ref>PMID:20159555</ref> <ref>PMID:22366786</ref> <ref>PMID:28233300</ref>

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== Publication Abstract from PubMed ==

DNAJB6 is a prime example of an anti-aggregation chaperone that functions as an oligomer. DNAJB6 oligomers are dynamic and subunit exchange is critical for inhibiting client protein aggregation. The T193A mutation in the C-terminal domain (CTD) of DNAJB6 reduces both chaperone self-oligomerization and anti-aggregation of client proteins, and has recently been linked to Parkinson's disease. Here, we show by NMR, including relaxation-based methods, that the T193A mutation has minimal effects on the structure of the beta-stranded CTD but increases the population and rate of formation of a partially folded state. The results can be rationalized in terms of beta-strand peptide plane flips that occur on a timescale of approximately 100 mus and lead to global changes in the overall pleat/flatness of the CTD, thereby altering its ability to oligomerize. These findings help forge a link between chaperone dynamics, oligomerization and anti-aggregation activity which may possibly lead to new therapeutic avenues tuned to target specific substrates.

Microsecond Backbone Motions Modulate the Oligomerization of the DNAJB6 Chaperone.,Cawood EE, Clore GM, Karamanos TK Angew Chem Int Ed Engl. 2022 Mar 5:e202116403. doi: 10.1002/anie.202116403. PMID:35247211<ref>PMID:35247211</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 7qby" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Cawood, E E]]

[[Category: Karamanos, T K]]

[[Category: Hsp40 chaperone]]