7jsq

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==Refined structure of the C-terminal domain of DNAJB6b==
==Refined structure of the C-terminal domain of DNAJB6b==
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<StructureSection load='7jsq' size='340' side='right'caption='[[7jsq]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
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<StructureSection load='7jsq' size='340' side='right'caption='[[7jsq]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[7jsq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JSQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7JSQ FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7jsq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JSQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JSQ FirstGlance]. <br>
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</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]]</div></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DNAJB6, HSJ2, MRJ, MSJ1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7jsq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jsq OCA], [https://pdbe.org/7jsq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jsq RCSB], [https://www.ebi.ac.uk/pdbsum/7jsq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jsq ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7jsq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jsq OCA], [http://pdbe.org/7jsq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7jsq RCSB], [http://www.ebi.ac.uk/pdbsum/7jsq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7jsq ProSAT]</span></td></tr>
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</table>
</table>
== Disease ==
== Disease ==
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[[http://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>
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[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 ==
== Function ==
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[[http://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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[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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Chaperone oligomerization is often a key aspect of their function. Irrespective of whether chaperone oligomers act as reservoirs for active monomers or exhibit a chaperoning function themselves, understanding the mechanism of oligomerization will further our understanding of how chaperones maintain the proteome. Here, we focus on the class-II Hsp40, human DNAJB6b, a highly efficient inhibitor of protein self-assembly in vivo and in vitro that forms functional oligomers. Using single-quantum methyl-based relaxation dispersion NMR methods we identify critical residues for DNAJB6b oligomerization in its C-terminal domain (CTD). Detailed solution NMR studies on the structure of the CTD showed that a serine/threonine-rich stretch causes a backbone twist in the N-terminal beta strand, stabilizing the monomeric form. Quantitative analysis of an array of NMR relaxation-based experiments (including Carr-Purcell-Meiboom-Gill relaxation dispersion, off-resonance R 1rho profiles, lifetime line broadening, and exchange-induced shifts) on the CTD of both wild type and a point mutant (T142A) within the S/T region of the first beta strand delineates the kinetics of the interconversion between the major twisted-monomeric conformation and a more regular beta strand configuration in an excited-state dimer, as well as exchange of both monomer and dimer species with high-molecular-weight oligomers. These data provide insights into the molecular origins of DNAJB6b oligomerization. Further, the results reported here have implications for the design of beta sheet proteins with tunable self-assembling properties and pave the way to an atomic-level understanding of amyloid inhibition.
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An S/T motif controls reversible oligomerization of the Hsp40 chaperone DNAJB6b through subtle reorganization of a beta sheet backbone.,Karamanos TK, Tugarinov V, Clore GM Proc Natl Acad Sci U S A. 2020 Dec 1;117(48):30441-30450. doi:, 10.1073/pnas.2020306117. Epub 2020 Nov 16. PMID:33199640<ref>PMID:33199640</ref>
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==See Also==
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*[[DnaJ homolog 3D structures|DnaJ homolog 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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*[[Heat Shock Protein structures|Heat Shock Protein structures]]
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</div>
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<div class="pdbe-citations 7jsq" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Clore, G M]]
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[[Category: Clore GM]]
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[[Category: Karamanos, T K]]
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[[Category: Karamanos TK]]
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[[Category: Anti-aggregation]]
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[[Category: Chaperone]]
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[[Category: Hsp40]]
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Current revision

Refined structure of the C-terminal domain of DNAJB6b

PDB ID 7jsq

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