5ofb
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human MORC2 (residues 1-603) with spinal muscular atrophy mutation S87L== | |
| + | <StructureSection load='5ofb' size='340' side='right' caption='[[5ofb]], [[Resolution|resolution]] 2.02Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5ofb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OFB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OFB FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5ofb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ofb OCA], [http://pdbe.org/5ofb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ofb RCSB], [http://www.ebi.ac.uk/pdbsum/5ofb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ofb ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/MORC2_HUMAN MORC2_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/MORC2_HUMAN MORC2_HUMAN]] Exhibits a cytosolic function in lipogenesis, adipogenic differentiation, and lipid homeostasis by increasing the activity of ACLY, possibly preventing its dephosphorylation (PubMed:24286864). May act as a transcriptional repressor (PubMed:20225202). Down-regulates CA9 expression (PubMed:20110259).<ref>PMID:20110259</ref> <ref>PMID:20225202</ref> <ref>PMID:24286864</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Dominant mutations in the MORC2 gene have recently been shown to cause axonal Charcot-Marie-Tooth (CMT) disease, but the cellular function of MORC2 is poorly understood. Here, through a genome-wide CRISPR-Cas9-mediated forward genetic screen, we identified MORC2 as an essential gene required for epigenetic silencing by the HUSH complex. HUSH recruits MORC2 to target sites in heterochromatin. We exploited a new method, differential viral accessibility (DIVA), to show that loss of MORC2 results in chromatin decompaction at these target loci, which is concomitant with a loss of H3K9me3 deposition and transcriptional derepression. The ATPase activity of MORC2 is critical for HUSH-mediated silencing, and the most common alteration affecting the ATPase domain in CMT patients (p.Arg252Trp) hyperactivates HUSH-mediated repression in neuronal cells. These data define a critical role for MORC2 in epigenetic silencing by the HUSH complex and provide a mechanistic basis underpinning the role of MORC2 mutations in CMT disease. | ||
| - | + | Hyperactivation of HUSH complex function by Charcot-Marie-Tooth disease mutation in MORC2.,Tchasovnikarova IA, Timms RT, Douse CH, Roberts RC, Dougan G, Kingston RE, Modis Y, Lehner PJ Nat Genet. 2017 Jul;49(7):1035-1044. doi: 10.1038/ng.3878. Epub 2017 Jun 5. PMID:28581500<ref>PMID:28581500</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5ofb" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Douse, C H]] | ||
| + | [[Category: Liu, Y]] | ||
| + | [[Category: Modis, Y]] | ||
| + | [[Category: Charcot-marie-tooth disease]] | ||
| + | [[Category: Chromatin remodeler]] | ||
| + | [[Category: Coiled-coil]] | ||
| + | [[Category: Cw domain]] | ||
| + | [[Category: Dna binding protein]] | ||
| + | [[Category: Epigenetic silencing]] | ||
| + | [[Category: Ghkl atpase]] | ||
| + | [[Category: Nuclear protein]] | ||
| + | [[Category: Spinal muscular atrophy]] | ||
| + | [[Category: Transcriptional repressor]] | ||
Revision as of 06:26, 15 February 2018
Crystal structure of human MORC2 (residues 1-603) with spinal muscular atrophy mutation S87L
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