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| | <StructureSection load='6mf6' size='340' side='right'caption='[[6mf6]], [[Resolution|resolution]] 3.40Å' scene=''> | | <StructureSection load='6mf6' size='340' side='right'caption='[[6mf6]], [[Resolution|resolution]] 3.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6mf6]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MF6 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6MF6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6mf6]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MF6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MF6 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDC5, MSD2, PKX2, YMR001C, YM8270.03C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), DBF4, DNA52, YDR052C, D4205, YD9609.07C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Polo_kinase Polo kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.21 2.7.11.21] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6mf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mf6 OCA], [https://pdbe.org/6mf6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mf6 RCSB], [https://www.ebi.ac.uk/pdbsum/6mf6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mf6 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6mf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mf6 OCA], [http://pdbe.org/6mf6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mf6 RCSB], [http://www.ebi.ac.uk/pdbsum/6mf6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mf6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CDC5_YEAST CDC5_YEAST]] Protein kinase required for the cell cycle where it is involved in mitotic exit. A component of the fear (CDC14 early anaphase release) network which promotes CDC14 release from the nucleolus during early anaphase. Phosphorylates SCC1/MCD1 and NET1.<ref>PMID:11371343</ref> <ref>PMID:11832211</ref> <ref>PMID:12056824</ref> [[http://www.uniprot.org/uniprot/DBF4_YEAST DBF4_YEAST]] Regulatory subunit of the CDC7-DBF4 kinase, also called DBF4-dependent kinase (DDK), which is involved in cell cycle regulation of premitotic and premeiotic chromosome replication and in chromosome segregation. DDK plays an essential role in initiating DNA replication at replication origins by phosphorylating the MCM2 and MCM4 subunits of the MCM2-7 helicase complex. DBF4 recruits the catalytic subunit CDC7 to MCM2 and to origins of replication. DDK has also postreplicative functions in meiosis. DDK phosphorylates the meiosis-specific double-strand break protein MER2 for initiation of meiotic recombination. Interacts with CDC5 during meiosis to promote double-strand breaks and monopolar spindle orientation. Inhibits CDC5 activity during mitosis through direct binding to its PBD.<ref>PMID:8066465</ref> <ref>PMID:12441400</ref> <ref>PMID:16319063</ref> <ref>PMID:17018296</ref> <ref>PMID:19013276</ref> <ref>PMID:18245450</ref> <ref>PMID:19692334</ref> <ref>PMID:19478884</ref> <ref>PMID:20436286</ref> <ref>PMID:21036905</ref> <ref>PMID:20170732</ref> <ref>PMID:20054399</ref> | + | [https://www.uniprot.org/uniprot/CDC5_YEAST CDC5_YEAST] Protein kinase required for the cell cycle where it is involved in mitotic exit. A component of the fear (CDC14 early anaphase release) network which promotes CDC14 release from the nucleolus during early anaphase. Phosphorylates SCC1/MCD1 and NET1.<ref>PMID:11371343</ref> <ref>PMID:11832211</ref> <ref>PMID:12056824</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Baker's yeast]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Polo kinase]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Almawi, A W]] | + | [[Category: Almawi AW]] |
| - | [[Category: Guarne, A]] | + | [[Category: Guarne A]] |
| - | [[Category: Cell cycle]]
| + | |
| - | [[Category: Dbf4]]
| + | |
| - | [[Category: Mitosis]]
| + | |
| - | [[Category: Polo-like kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
CDC5_YEAST Protein kinase required for the cell cycle where it is involved in mitotic exit. A component of the fear (CDC14 early anaphase release) network which promotes CDC14 release from the nucleolus during early anaphase. Phosphorylates SCC1/MCD1 and NET1.[1] [2] [3]
Publication Abstract from PubMed
Polo-like kinases (Plks) are key cell cycle regulators. They contain a kinase domain followed by a polo-box domain that recognizes phosphorylated substrates and enhances their phosphorylation. The regulatory subunit of the Dbf4-dependent kinase complex interacts with the polo-box domain of Cdc5 (the sole Plk in Saccharomyces cerevisiae) in a phosphorylation-independent manner. We have solved the crystal structures of the polo-box domain of Cdc5 on its own and in the presence of peptides derived from Dbf4 and a canonical phosphorylated substrate. The structure bound to the Dbf4-peptide reveals an additional density on the surface opposite to the phospho-peptide binding site that allowed us to propose a model for the interaction. We found that the two peptides can bind simultaneously and non-competitively to the polo-box domain in solution. Furthermore, point mutations on the surface opposite to the phosphopeptide binding site of the polo-box domain disrupt the interaction with the Dbf4 peptide in solution and cause an early anaphase arrest phenotype distinct from the mitotic exit defect typically observed in cdc5 mutants. Collectively, our data illustrates the importance of non-canonical interactions mediated by the polo-box domain and provide key mechanistic insights into the combinatorial recognition of substrates by Polo-like kinases.
Distinct surfaces on Cdc5/PLK Polo-box domain orchestrate combinatorial substrate recognition during cell division.,Almawi AW, Langlois-Lemay L, Boulton S, Rodriguez Gonzalez J, Melacini G, D'Amours D, Guarne A Sci Rep. 2020 Feb 25;10(1):3379. doi: 10.1038/s41598-020-60344-4. PMID:32099015[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Alexandru G, Uhlmann F, Mechtler K, Poupart MA, Nasmyth K. Phosphorylation of the cohesin subunit Scc1 by Polo/Cdc5 kinase regulates sister chromatid separation in yeast. Cell. 2001 May 18;105(4):459-72. PMID:11371343
- ↑ Stegmeier F, Visintin R, Amon A. Separase, polo kinase, the kinetochore protein Slk19, and Spo12 function in a network that controls Cdc14 localization during early anaphase. Cell. 2002 Jan 25;108(2):207-20. PMID:11832211
- ↑ Yoshida S, Toh-e A. Budding yeast Cdc5 phosphorylates Net1 and assists Cdc14 release from the nucleolus. Biochem Biophys Res Commun. 2002 Jun 14;294(3):687-91. doi:, 10.1016/S0006-291X(02)00544-2. PMID:12056824 doi:http://dx.doi.org/10.1016/S0006-291X(02)00544-2
- ↑ Almawi AW, Langlois-Lemay L, Boulton S, Rodriguez Gonzalez J, Melacini G, D'Amours D, Guarne A. Distinct surfaces on Cdc5/PLK Polo-box domain orchestrate combinatorial substrate recognition during cell division. Sci Rep. 2020 Feb 25;10(1):3379. doi: 10.1038/s41598-020-60344-4. PMID:32099015 doi:http://dx.doi.org/10.1038/s41598-020-60344-4
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