View source for 9rux


==Cryo-EM structure of DISC1 core==
<StructureSection load='9rux' size='340' side='right'caption='[[9rux]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9rux]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9RUX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9RUX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.9&#8491;</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=9rux FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9rux OCA], [https://pdbe.org/9rux PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9rux RCSB], [https://www.ebi.ac.uk/pdbsum/9rux PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9rux ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DISC1_MOUSE DISC1_MOUSE] Involved in the regulation of multiple aspects of embryonic and adult neurogenesis. Required for neural progenitor proliferation in the ventrical/subventrical zone during embryonic brain development and in the adult dentate gyrus of the hippocampus. Participates in the Wnt-mediated neural progenitor proliferation as a positive regulator by modulating GSK3B activity and CTNNB1 abundance. Plays a role as a modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including neuron positioning, dendritic development and synapse formation. Inhibits the activation of AKT-mTOR signaling upon interaction with CCDC88A. Regulates the migration of early-born granule cell precursors toward the dentate gyrus during the hippocampal development. Plays a role, together with PCNT, in the microtubule network formation.<ref>PMID:17825401</ref> <ref>PMID:19303846</ref> <ref>PMID:19502360</ref> <ref>PMID:19778506</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
DISC1 is a pleiotropic protein with essential roles in neuronal proliferation and migration, intracellular signalling and cargo transport. It associates with a diverse array of partner molecules in these contexts. Mutations at the DISC1 locus are strongly associated with a spectrum of mental illnesses such as schizophrenia and depression. Despite its clinical relevance, the molecular architecture and function of DISC1 have remained largely elusive. We present a cryo-EM structure of the entire conserved core region of DISC1. The structure reveals an intricate homotetrameric assembly that harbours conserved bacteria-derived UVR domains. Four of these domains, one from each monomer, mediate extensive contacts forming two asymmetric dimer units. The dimers in turn interface with each other at two distinct coiled coil domains to achieve a two-fold symmetric tetramer. Mutational analysis shows that this tetrameric architecture enables DISC1 to simultaneously bind multiple copies of NDE1 client protein. Importantly, tetramerization and partner binding are structurally independent functions of DISC1. Altogether, our study provides a compelling molecular model of an ancient bacteria protein fold participating in the assembly of a multivalent mammalian scaffold hub that can coordinate multiple partner molecules.

The schizophrenia associated protein DISC1 forms a multivalent tetrameric hub via conserved UVR dimers.,Zhou JC, Kratochvil J, Ye F, El Omari K, Kukura P, Zhang M, Seiradake E Nat Commun. 2026 Apr 17. doi: 10.1038/s41467-026-71838-6. PMID:41997921<ref>PMID:41997921</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9rux" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Zhou JC]]