View source for 5vsz


==Structure of the Ubl domain of Sacsin mutant L78M==
<StructureSection load='5vsz' size='340' side='right'caption='[[5vsz]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5vsz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VSZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VSZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=5vsz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vsz OCA], [https://pdbe.org/5vsz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vsz RCSB], [https://www.ebi.ac.uk/pdbsum/5vsz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vsz ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SACS_HUMAN SACS_HUMAN] Defects in SACS are the cause of spastic ataxia Charlevoix-Saguenay type (SACS) [MIM:[https://omim.org/entry/270550 270550]. It is a neurodegenerative disease characterized by early-onset cerebellar ataxia, spasticity, retinal hypermyelination, pyramidal signs, and both axonal and demyelinating neuropathy with loss of sensory nerve conduction and reduced motor conduction velocities. Other features include dysarthria, distal muscle wasting, nystagmus, defect in conjugate pursuit ocular movements, retinal striation (from prominent retinal nerves) obscuring the retinal blood vessels in places, and the frequent presence of mitral valve prolapse.<ref>PMID:10655055</ref> <ref>PMID:19529988</ref> <ref>PMID:12873855</ref> <ref>PMID:15156359</ref> <ref>PMID:14718708</ref> <ref>PMID:16007637</ref> <ref>PMID:15985586</ref> <ref>PMID:17290461</ref> <ref>PMID:18398442</ref> <ref>PMID:18484239</ref> <ref>PMID:17716690</ref> <ref>PMID:18465152</ref> <ref>PMID:20876471</ref> 
== Function ==
[https://www.uniprot.org/uniprot/SACS_HUMAN SACS_HUMAN] Co-chaperone which acts as a regulator of the Hsp70 chaperone machinery and may be involved in the processing of other ataxia-linked proteins.<ref>PMID:19208651</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disease that is caused by mutations in the SACS gene. The product of this gene is a very large 520 kDa cytoplasmic protein, sacsin, with an ubiquitin-like domain (Ubl) at the N-terminus followed by three large sacsin internal repeats (SIRPTs) supradomains and C-terminal J and HEPN domains. The SIRPTs are predicted to contain Hsp90-like domains suggesting a potential chaperone activity. In this work, we report the structures of the Hsp90-like Sr1 domain of SIRPT1 and the N-terminal Ubl domain determined at 1.55 A and 2.1 A resolution, respectively. The Ubl domain crystallized as a swapped dimer that could be relevant in the context of full-length protein. The Sr1 domain displays the Bergerat protein fold with a characteristic nucleotide-binding pocket, though it binds nucleotides with very low affinity. The Sr1 structure reveals that ARSACS-causing missense mutations (R272H, R272C and T201K) disrupt protein folding most likely leading to sacsin degradation. This work lends a structural support to the view of sacsin as a molecular chaperone and provides a framework for future studies of this protein.

Structures of Ubl and Hsp90-like domains of sacsin provide insight into pathological mutations.,Menade M, Kozlov G, Trempe JF, Pande H, Shenker S, Wickremasinghe S, Li X, Hojjat H, Dicaire MJ, Brais B, McPherson PS, Wong MJH, Young JC, Gehring K J Biol Chem. 2018 Jun 26. pii: RA118.003939. doi: 10.1074/jbc.RA118.003939. PMID:29945973<ref>PMID:29945973</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5vsz" style="background-color:#fffaf0;"></div>

==See Also==
*[[DnaJ homolog 3D structures|DnaJ homolog 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gehring K]]
[[Category: Pande H]]
[[Category: Shenker S]]
[[Category: Trempe J-F]]