7qby
From Proteopedia
(Difference between revisions)
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==Refined structure of the T193A mutant in the C-terminal domain of DNAJB6b== | ==Refined structure of the T193A mutant in the C-terminal domain of DNAJB6b== | ||
| - | <StructureSection load='7qby' size='340' side='right'caption='[[7qby]]' scene=''> | + | <StructureSection load='7qby' size='340' side='right'caption='[[7qby]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full | + | <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='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> | + | </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> | ||
</table> | </table> | ||
| + | == 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7qby" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Cawood | + | [[Category: Cawood, E E]] |
| - | [[Category: Karamanos | + | [[Category: Karamanos, T K]] |
| + | [[Category: Anti-aggregation]] | ||
| + | [[Category: Chaperone]] | ||
| + | [[Category: Hsp40 chaperone]] | ||
Revision as of 06:32, 12 May 2022
Refined structure of the T193A mutant in the C-terminal domain of DNAJB6b
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