5of9: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5of9 is ON HOLD  until Paper Publication
+==Crystal structure of human MORC2 (residues 1-603)==
+<StructureSection load='5of9' size='340' side='right' caption='[[5of9]], [[Resolution|resolution]] 1.81&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5of9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OF9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OF9 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</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=5of9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5of9 OCA], [http://pdbe.org/5of9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5of9 RCSB], [http://www.ebi.ac.uk/pdbsum/5of9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5of9 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.
-Authors:
+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>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5of9" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Douse, C H]]
+[[Category: Modis, Y]]
+[[Category: Shamin, M]]
+[[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]]