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| - | [[Image:1nex.gif|left|200px]] | |
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| - | <!--
| + | ==Crystal Structure of ScSkp1-ScCdc4-CPD peptide complex== |
| - | The line below this paragraph, containing "STRUCTURE_1nex", creates the "Structure Box" on the page.
| + | <StructureSection load='1nex' size='340' side='right'caption='[[1nex]], [[Resolution|resolution]] 2.70Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[1nex]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NEX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NEX FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display. | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | -->
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> |
| - | {{STRUCTURE_1nex| PDB=1nex | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nex FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nex OCA], [https://pdbe.org/1nex PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nex RCSB], [https://www.ebi.ac.uk/pdbsum/1nex PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nex ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/SKP1_YEAST SKP1_YEAST] Essential component of the E3 ubiquitin ligase complex SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins like phosphorylated SIC1. Participates in the attachment of chromosomes to the spindle. Acts as a regulatory component of the centromere DNA-binding protein complex CBF3, which is essential for chromosome segregation and movement of centromeres along microtubules. CBF3 is required for the recruitment of other kinetochore complexes to CEN DNA. It plays a role in the attachment of chromosomes to the spindle and binds selectively to a highly conserved DNA sequence called CDEIII, found in centromeres and in several promoters. The association of CBF3C with CBF3D and SGT1 is required for CBF3C activation and CBF3 assembly. SKP1/CBF3D could retrieve cyclins or cyclin-CDK-like proteins into the kinetochore thus providing cell cycle-regulated kinetochore activity. Involved in the regulation of methionine biosynthesis genes. Facilitates association of CDC53 with CDC4 and of ROY1 with YPT52.<ref>PMID:8706132</ref> <ref>PMID:8706131</ref> <ref>PMID:9346238</ref> <ref>PMID:9346239</ref> <ref>PMID:21389113</ref> <ref>PMID:9499404</ref> <ref>PMID:17517885</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ne/1nex_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1nex ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | '''Crystal Structure of ScSkp1-ScCdc4-CPD peptide complex'''
| + | ==See Also== |
| - | | + | *[[Centromere protein 3D structure|Centromere protein 3D structure]] |
| - | | + | == References == |
| - | ==Overview== | + | <references/> |
| - | Cell cycle progression depends on precise elimination of cyclins and cyclin-dependent kinase (CDK) inhibitors by the ubiquitin system. Elimination of the CDK inhibitor Sic1 by the SCFCdc4 ubiquitin ligase at the onset of S phase requires phosphorylation of Sic1 on at least six of its nine Cdc4-phosphodegron (CPD) sites. A 2.7 A X-ray crystal structure of a Skp1-Cdc4 complex bound to a high-affinity CPD phosphopeptide from human cyclin E reveals a core CPD motif, Leu-Leu-pThr-Pro, bound to an eight-bladed WD40 propeller domain in Cdc4. The low affinity of each CPD motif in Sic1 reflects structural discordance with one or more elements of the Cdc4 binding site. Reengineering of Cdc4 to reduce selection against Sic1 sequences allows ubiquitination of lower phosphorylated forms of Sic1. These features account for the observed phosphorylation threshold in Sic1 recognition and suggest an equilibrium binding mode between a single receptor site in Cdc4 and multiple low-affinity CPD sites in Sic1.
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==About this Structure==
| + | [[Category: Large Structures]] |
| - | 1NEX is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NEX OCA].
| + | |
| - | | + | |
| - | ==Reference== | + | |
| - | Structural basis for phosphodependent substrate selection and orientation by the SCFCdc4 ubiquitin ligase., Orlicky S, Tang X, Willems A, Tyers M, Sicheri F, Cell. 2003 Jan 24;112(2):243-56. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12553912 12553912]
| + | |
| - | [[Category: Protein complex]] | + | |
| | [[Category: Saccharomyces cerevisiae]] | | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Orlicky, S.]] | + | [[Category: Orlicky S]] |
| - | [[Category: Sicheri, F.]] | + | [[Category: Sicheri F]] |
| - | [[Category: Tang, X.]] | + | [[Category: Tang X]] |
| - | [[Category: Tyers, M.]] | + | [[Category: Tyers M]] |
| - | [[Category: Willems, A.]] | + | [[Category: Willems A]] |
| - | [[Category: E3 ubiquitin ligase]]
| + | |
| - | [[Category: Phospho-peptide complex]]
| + | |
| - | [[Category: Wd 40 domain]]
| + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 02:26:57 2008''
| + | |
| Structural highlights
Function
SKP1_YEAST Essential component of the E3 ubiquitin ligase complex SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins like phosphorylated SIC1. Participates in the attachment of chromosomes to the spindle. Acts as a regulatory component of the centromere DNA-binding protein complex CBF3, which is essential for chromosome segregation and movement of centromeres along microtubules. CBF3 is required for the recruitment of other kinetochore complexes to CEN DNA. It plays a role in the attachment of chromosomes to the spindle and binds selectively to a highly conserved DNA sequence called CDEIII, found in centromeres and in several promoters. The association of CBF3C with CBF3D and SGT1 is required for CBF3C activation and CBF3 assembly. SKP1/CBF3D could retrieve cyclins or cyclin-CDK-like proteins into the kinetochore thus providing cell cycle-regulated kinetochore activity. Involved in the regulation of methionine biosynthesis genes. Facilitates association of CDC53 with CDC4 and of ROY1 with YPT52.[1] [2] [3] [4] [5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ Connelly C, Hieter P. Budding yeast SKP1 encodes an evolutionarily conserved kinetochore protein required for cell cycle progression. Cell. 1996 Jul 26;86(2):275-85. PMID:8706132
- ↑ Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ. SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell. 1996 Jul 26;86(2):263-74. PMID:8706131
- ↑ Skowyra D, Craig KL, Tyers M, Elledge SJ, Harper JW. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. Cell. 1997 Oct 17;91(2):209-19. PMID:9346238
- ↑ Feldman RM, Correll CC, Kaplan KB, Deshaies RJ. A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p. Cell. 1997 Oct 17;91(2):221-30. PMID:9346239
- ↑ Liu Y, Nakatsukasa K, Kotera M, Kanada A, Nishimura T, Kishi T, Mimura S, Kamura T. Non-SCF-type F-box protein Roy1/Ymr258c interacts with a Rab5-like GTPase Ypt52 and inhibits Ypt52 function. Mol Biol Cell. 2011 May;22(9):1575-84. doi: 10.1091/mbc.E10-08-0716. Epub 2011, Mar 9. PMID:21389113 doi:10.1091/mbc.E10-08-0716
- ↑ Patton EE, Willems AR, Sa D, Kuras L, Thomas D, Craig KL, Tyers M. Cdc53 is a scaffold protein for multiple Cdc34/Skp1/F-box proteincomplexes that regulate cell division and methionine biosynthesis in yeast. Genes Dev. 1998 Mar 1;12(5):692-705. PMID:9499404
- ↑ Escusa S, Laporte D, Massoni A, Boucherie H, Dautant A, Daignan-Fornier B. Skp1-Cullin-F-box-dependent degradation of Aah1p requires its interaction with the F-box protein Saf1p. J Biol Chem. 2007 Jul 13;282(28):20097-103. Epub 2007 May 21. PMID:17517885 doi:10.1074/jbc.M702425200
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