This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


7jsq

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
==Refined structure of the C-terminal domain of DNAJB6b==
==Refined structure of the C-terminal domain of DNAJB6b==
-
<StructureSection load='7jsq' size='340' side='right'caption='[[7jsq]]' scene=''>
+
<StructureSection load='7jsq' size='340' side='right'caption='[[7jsq]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>Full crystallographic 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>
+
<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>
-
</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=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>
+
</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>
 +
<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>
 +
<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>
</table>
</table>
 +
== Disease ==
 +
[[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>
 +
== Function ==
 +
[[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>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
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.
 +
 +
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>
 +
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 7jsq" style="background-color:#fffaf0;"></div>
 +
== References ==
 +
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
 +
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: Clore GM]]
+
[[Category: Clore, G M]]
-
[[Category: Karamanos TK]]
+
[[Category: Karamanos, T K]]
 +
[[Category: Anti-aggregation]]
 +
[[Category: Chaperone]]
 +
[[Category: Hsp40]]

Revision as of 13:01, 16 December 2020

Refined structure of the C-terminal domain of DNAJB6b

PDB ID 7jsq

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7jsq"
Personal tools