5vzu

From Proteopedia

(Difference between revisions)

Revision as of 09:43, 1 January 2020

Crystal structure of the Skp1-FBXO31-cyclin D1 complex

Structural highlights

5vzu is a 6 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:	5vzt
Gene:	SKP1, EMC19, OCP2, SKP1A, TCEB1L (HUMAN), FBXO31, FBX14, FBX31, PP2386 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[FBX31_HUMAN] Autosomal recessive non-syndromic intellectual disability. The disease is caused by mutations affecting the gene represented in this entry.

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] [FBX31_HUMAN] Component of some SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in G1 arrest following DNA damage. Specifically recognizes phosphorylated cyclin-D1 (CCND1), promoting its ubiquitination and degradation by the proteasome, resulting in G1 arrest. May act as a tumor suppressor.^[3] ^[4]

Publication Abstract from PubMed

Ubiquitin-dependent proteolysis of cyclin D1 is associated with normal and tumor cell proliferation and survival. The SCF(FBXO31) (Skp1-Cul1-Rbx1-FBXO31) ubiquitin ligase complex mediates genotoxic stress-induced cyclin D1 degradation. Previous studies have suggested that cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm. Here we present the crystal structures of the Skp1-FBXO31 complex alone and bound to a phosphorylated cyclin D1 C-terminal peptide. FBXO31 possesses a unique substrate-binding domain consisting of two beta-barrel motifs, whereas cyclin D1 binds to FBXO31 by tucking its free C-terminal carboxylate tail into an open cavity of the C-terminal FBXO31 beta-barrel. Biophysical and functional studies demonstrate that SCF(FBXO31) is capable of recruiting and ubiquitinating cyclin D1 in a phosphorylation-independent manner. Our findings provide a conceptual framework for understanding the substrate specificity of the F-box protein FBXO31 and the mechanism of FBXO31-regulated cyclin D1 protein turnover.

Structural basis of the phosphorylation-independent recognition of cyclin D1 by the SCF(FBXO31) ubiquitin ligase.,Li Y, Jin K, Bunker E, Zhang X, Luo X, Liu X, Hao B Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):319-324. doi:, 10.1073/pnas.1708677115. Epub 2017 Dec 26. PMID:29279382^[5]

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
↑ Kumar R, Neilsen PM, Crawford J, McKirdy R, Lee J, Powell JA, Saif Z, Martin JM, Lombaerts M, Cornelisse CJ, Cleton-Jansen AM, Callen DF. FBXO31 is the chromosome 16q24.3 senescence gene, a candidate breast tumor suppressor, and a component of an SCF complex. Cancer Res. 2005 Dec 15;65(24):11304-13. doi: 10.1158/0008-5472.CAN-05-0936. PMID:16357137 doi:http://dx.doi.org/10.1158/0008-5472.CAN-05-0936
↑ Santra MK, Wajapeyee N, Green MR. F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage. Nature. 2009 Jun 4;459(7247):722-5. Epub 2009 May 3. PMID:19412162 doi:http://dx.doi.org/nature08011
↑ Li Y, Jin K, Bunker E, Zhang X, Luo X, Liu X, Hao B. Structural basis of the phosphorylation-independent recognition of cyclin D1 by the SCF(FBXO31) ubiquitin ligase. Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):319-324. doi:, 10.1073/pnas.1708677115. Epub 2017 Dec 26. PMID:29279382 doi:http://dx.doi.org/10.1073/pnas.1708677115

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Crystal structure of the Skp1-FBXO31-cyclin D1 complex==
-<StructureSection load='5vzu' size='340' side='right' caption='[[5vzu]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+<StructureSection load='5vzu' size='340' side='right'caption='[[5vzu]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5vzu]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VZU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VZU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5vzu]] is a 6 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=5VZU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VZU FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vzt|5vzt]]</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]), FBXO31, FBX14, FBX31, PP2386 ([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=5vzu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vzu OCA], [http://pdbe.org/5vzu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vzu RCSB], [http://www.ebi.ac.uk/pdbsum/5vzu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vzu ProSAT]</span></td></tr>
 </table>
@@ Line 26: / Line 27: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Hao, B]]
 [[Category: Jin, K]]

5vzu

From Proteopedia

Revision as of 09:43, 1 January 2020

Crystal structure of the Skp1-FBXO31-cyclin D1 complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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