5yi4
From Proteopedia
(Difference between revisions)
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==Solution Structure of the DISC1/Ndel1 complex== | ==Solution Structure of the DISC1/Ndel1 complex== | ||
| - | <StructureSection load='5yi4' size='340' side='right' caption='[[5yi4]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='5yi4' size='340' side='right'caption='[[5yi4]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5yi4]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YI4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YI4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5yi4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YI4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YI4 FirstGlance]. <br> |
| - | </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=5yi4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yi4 OCA], [http://pdbe.org/5yi4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yi4 RCSB], [http://www.ebi.ac.uk/pdbsum/5yi4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yi4 ProSAT]</span></td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ndel1, Nudel ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5yi4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yi4 OCA], [http://pdbe.org/5yi4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yi4 RCSB], [http://www.ebi.ac.uk/pdbsum/5yi4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yi4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://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> | [[http://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 == | ||
| + | Mutations of DISC1 (disrupted-in-schizophrenia 1) have been associated with major psychiatric disorders. Despite the hundreds of DISC1-binding proteins reported, almost nothing is known about how DISC1 interacts with other proteins structurally to impact human brain development. Here we solved the high-resolution structure of DISC1 C-terminal tail in complex with its binding domain of Ndel1. Mechanistically, DISC1 regulates Ndel1's kinetochore attachment, but not its centrosome localization, during mitosis. Functionally, disrupting DISC1/Ndel1 complex formation prolongs mitotic length and interferes with cell-cycle progression in human cells, and it causes cell-cycle deficits of radial glial cells in the embryonic mouse cortex and human forebrain organoids. We also observed similar deficits in organoids derived from schizophrenia patient induced pluripotent stem cells (iPSCs) with a DISC1 mutation that disrupts its interaction with Ndel1. Our study uncovers a new mechanism of action for DISC1 based on its structure, and it has implications for how genetic insults may contribute to psychiatric disorders. | ||
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| + | DISC1 Regulates Neurogenesis via Modulating Kinetochore Attachment of Ndel1/Nde1 during Mitosis.,Ye F, Kang E, Yu C, Qian X, Jacob F, Yu C, Mao M, Poon RYC, Kim J, Song H, Ming GL, Zhang M Neuron. 2017 Dec 6;96(5):1041-1054.e5. doi: 10.1016/j.neuron.2017.10.010. Epub, 2017 Nov 2. PMID:29103808<ref>PMID:29103808</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5yi4" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Lk3 transgenic mice]] | ||
[[Category: Ye, F]] | [[Category: Ye, F]] | ||
[[Category: Yu, C]] | [[Category: Yu, C]] | ||
Revision as of 06:30, 29 May 2019
Solution Structure of the DISC1/Ndel1 complex
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