5v4b
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the Skp1-FBXW7-DISC1 complex== | |
| + | <StructureSection load='5v4b' size='340' side='right' caption='[[5v4b]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5v4b]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V4B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V4B FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ovp|2ovp]], [[2ovq|2ovq]], [[2ovr|2ovr]]</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=5v4b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v4b OCA], [http://pdbe.org/5v4b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v4b RCSB], [http://www.ebi.ac.uk/pdbsum/5v4b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v4b ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/SKP1_HUMAN SKP1_HUMAN]] Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110.<ref>PMID:16209941</ref> <ref>PMID:20181953</ref> [[http://www.uniprot.org/uniprot/FBXW7_HUMAN FBXW7_HUMAN]] Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Probably recognizes and binds to phosphorylated target proteins. Involved in the degradation of cyclin-E, MYC, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1.<ref>PMID:11565034</ref> <ref>PMID:11585921</ref> <ref>PMID:15103331</ref> <ref>PMID:17873522</ref> <ref>PMID:17558397</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Disrupted in schizophrenia 1 (DISC1) is a multi-functional scaffolding protein that has been associated with neuropsychiatric disease. The role of DISC1 is to assemble protein complexes that promote neural development and signaling, hence tight control of the concentration of cellular DISC1 in neurons is vital to brain function. Using structural and biochemical techniques, we show for we believe the first time that not only is DISC1 turnover elicited by the ubiquitin proteasome system (UPS) but that it is orchestrated by the F-Box protein, FBXW7. We present the structure of FBXW7 bound to the DISC1 phosphodegron motif and exploit this information to prove that disruption of the FBXW7-DISC1 complex results in a stabilization of DISC1. This action can counteract DISC1 deficiencies observed in neural progenitor cells derived from induced pluripotent stem cells from schizophrenia patients with a DISC1 frameshift mutation. Thus manipulation of DISC1 levels via the UPS may provide a novel method to explore DISC1 function.Molecular Psychiatry advance online publication, 20 July 2017; doi:10.1038/mp.2017.138. | ||
| - | + | FBXW7 regulates DISC1 stability via the ubiquitin-proteosome system.,Yalla K, Elliott C, Day JP, Findlay J, Barratt S, Hughes ZA, Wilson L, Whiteley E, Popiolek M, Li Y, Dunlop J, Killick R, Adams DR, Brandon NJ, Houslay MD, Hao B, Baillie GS Mol Psychiatry. 2017 Jul 20. doi: 10.1038/mp.2017.138. PMID:28727686<ref>PMID:28727686</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 5v4b" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Baillie, G S]] | ||
[[Category: Hao, B]] | [[Category: Hao, B]] | ||
| - | [[Category: | + | [[Category: Li, Y]] |
| + | [[Category: Transcription]] | ||
| + | [[Category: Transcription-cell c complex]] | ||
| + | [[Category: Ubiquitin ligase/psychiatric disorder]] | ||
Revision as of 04:34, 21 September 2017
Crystal structure of the Skp1-FBXW7-DISC1 complex
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