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5v4b

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Revision as of 05:53, 16 May 2018

Crystal structure of the Skp1-FBXW7-DISC1 complex

Structural highlights

5v4b is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:	,
Related:	2ovp, 2ovq, 2ovr
Gene:	SKP1, EMC19, OCP2, SKP1A, TCEB1L (HUMAN), FBXW7, FBW7, FBX30, SEL10 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] [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.^[3] ^[4] ^[5] ^[6] ^[7]

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^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hao B, Zheng N, Schulman BA, Wu G, Miller JJ, Pagano M, Pavletich NP. Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase. Mol Cell. 2005 Oct 7;20(1):9-19. PMID:16209941 doi:10.1016/j.molcel.2005.09.003
↑ Li Y, Hao B. Structural basis of dimerization-dependent ubiquitination by the SCF(Fbx4) ubiquitin ligase. J Biol Chem. 2010 Apr 30;285(18):13896-906. Epub 2010 Feb 24. PMID:20181953 doi:10.1074/jbc.M110.111518
↑ Strohmaier H, Spruck CH, Kaiser P, Won KA, Sangfelt O, Reed SI. Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Nature. 2001 Sep 20;413(6853):316-22. PMID:11565034 doi:http://dx.doi.org/10.1038/35095076
↑ Wu G, Lyapina S, Das I, Li J, Gurney M, Pauley A, Chui I, Deshaies RJ, Kitajewski J. SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation. Mol Cell Biol. 2001 Nov;21(21):7403-15. PMID:11585921 doi:http://dx.doi.org/10.1128/MCB.21.21.7403-7415.2001
↑ Yada M, Hatakeyama S, Kamura T, Nishiyama M, Tsunematsu R, Imaki H, Ishida N, Okumura F, Nakayama K, Nakayama KI. Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J. 2004 May 19;23(10):2116-25. Epub 2004 Apr 22. PMID:15103331 doi:http://dx.doi.org/10.1038/sj.emboj.7600217
↑ Popov N, Herold S, Llamazares M, Schulein C, Eilers M. Fbw7 and Usp28 regulate myc protein stability in response to DNA damage. Cell Cycle. 2007 Oct 1;6(19):2327-31. Epub 2007 Jul 26. PMID:17873522
↑ Popov N, Wanzel M, Madiredjo M, Zhang D, Beijersbergen R, Bernards R, Moll R, Elledge SJ, Eilers M. The ubiquitin-specific protease USP28 is required for MYC stability. Nat Cell Biol. 2007 Jul;9(7):765-74. Epub 2007 Jun 10. PMID:17558397 doi:http://dx.doi.org/10.1038/ncb1601
↑ 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. FBXW7 regulates DISC1 stability via the ubiquitin-proteosome system. Mol Psychiatry. 2017 Jul 20. doi: 10.1038/mp.2017.138. PMID:28727686 doi:http://dx.doi.org/10.1038/mp.2017.138

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5v4b"

@@ Line 3: / Line 3: @@
 <StructureSection load='5v4b' size='340' side='right' caption='[[5v4b]], [[Resolution|resolution]] 2.60&Aring;' 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>
+<table><tr><td colspan='2'>[[5v4b]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SKP1, EMC19, OCP2, SKP1A, TCEB1L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), FBXW7, FBW7, FBX30, SEL10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Baillie, G S]]
 [[Category: Hao, B]]

5v4b

From Proteopedia

Revision as of 05:53, 16 May 2018

Crystal structure of the Skp1-FBXW7-DISC1 complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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