6nhk: Difference between revisions
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==Mortalin nucleotide binding domain in the ADP-bound state== | |||
<StructureSection load='6nhk' size='340' side='right'caption='[[6nhk]], [[Resolution|resolution]] 2.78Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6nhk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NHK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NHK FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6nhk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nhk OCA], [http://pdbe.org/6nhk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nhk RCSB], [http://www.ebi.ac.uk/pdbsum/6nhk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nhk ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/GRP75_HUMAN GRP75_HUMAN]] Implicated in the control of cell proliferation and cellular aging. May also act as a chaperone. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
HSPA9, the gene coding for the mitochondrial chaperone mortalin, is involved in various cellular roles such as mitochondrial protein import, folding, degradation, Fe-S cluster biogenesis, mitochondrial homeostasis, and regulation of the antiapoptotic protein p53. Mutations in the HSPA9 gene, particularly within the region coding for the nucleotide-binding domain (NBD), cause the autosomal disorder known as EVEN-PLUS syndrome. The resulting mutants R126W and Y128C are located on the surface of the mortalin-NBD near the binding interface with the interdomain linker (IDL). We used differential scanning fluorimetry (DSF), biolayer interferometry, X-ray crystallography, ATP hydrolysis assays, and Rosetta docking simulations to study the structural and functional consequences of the EVEN-PLUS syndrome-associated R126W and Y128C mutations within the mortalin-NBD. These results indicate that the surface mutations R126W and Y128C have far-reaching effects that disrupt ATP hydrolysis, interdomain linker binding, and thermostability and increase the propensity for aggregation. The structural differences observed provide insight into how the conformations of mortalin differ from other heat shock protein 70 (Hsp70) homologues. Combined, our biophysical and structural studies contribute to the understanding of the molecular basis for how disease-associated mortalin mutations affect mortalin functionality and the pathogenesis of EVEN-PLUS syndrome. | |||
Biophysical Consequences of EVEN-PLUS Syndrome Mutations for the Function of Mortalin.,Moseng MA, Nix JC, Page RC J Phys Chem B. 2019 Apr 12. doi: 10.1021/acs.jpcb.9b00071. PMID:30933555<ref>PMID:30933555</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6nhk" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Page, R | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Moseng, M A]] | |||
[[Category: Nix, J C]] | |||
[[Category: Page, R C]] | |||
[[Category: Chaperone]] | |||
[[Category: Hsp70]] | |||
[[Category: Mitochondrial]] | |||