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| | ==The Structure of the Plk4 Cryptic Polo Box Reveals Two Tandem Polo Boxes Required for Centriole Duplication== | | ==The Structure of the Plk4 Cryptic Polo Box Reveals Two Tandem Polo Boxes Required for Centriole Duplication== |
| - | <StructureSection load='4g7n' size='340' side='right' caption='[[4g7n]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='4g7n' size='340' side='right'caption='[[4g7n]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4g7n]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G7N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G7N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4g7n]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G7N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G7N FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 2.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CG7186, Plk4, SAK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 Drosophila melanogaster])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4g7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g7n OCA], [https://pdbe.org/4g7n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g7n RCSB], [https://www.ebi.ac.uk/pdbsum/4g7n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g7n ProSAT]</span></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=4g7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g7n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4g7n RCSB], [http://www.ebi.ac.uk/pdbsum/4g7n PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PLK4_DROME PLK4_DROME]] Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the mother centriole cylinder, using mother centriole as a platform, leading to the recruitment of centriole biogenesis proteins such as Sas-6. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Centrosome amplification following overexpression can initiate tumorigenesis, highlighting the importance of centrosome regulation in cancers.<ref>PMID:16326102</ref> <ref>PMID:17463247</ref> <ref>PMID:18555779</ref> | + | [https://www.uniprot.org/uniprot/PLK4_DROME PLK4_DROME] Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the mother centriole cylinder, using mother centriole as a platform, leading to the recruitment of centriole biogenesis proteins such as Sas-6. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Centrosome amplification following overexpression can initiate tumorigenesis, highlighting the importance of centrosome regulation in cancers.<ref>PMID:16326102</ref> <ref>PMID:17463247</ref> <ref>PMID:18555779</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4g7n" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Drosophila melanogaster]] | | [[Category: Drosophila melanogaster]] |
| - | [[Category: Polo kinase]] | + | [[Category: Large Structures]] |
| - | [[Category: Slep, K C]] | + | [[Category: Slep KC]] |
| - | [[Category: Slevin, L K]] | + | [[Category: Slevin LK]] |
| - | [[Category: Asterless]]
| + | |
| - | [[Category: Centriole]]
| + | |
| - | [[Category: Kinase targeting and regulation]]
| + | |
| - | [[Category: Polo box]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
PLK4_DROME Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the mother centriole cylinder, using mother centriole as a platform, leading to the recruitment of centriole biogenesis proteins such as Sas-6. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Centrosome amplification following overexpression can initiate tumorigenesis, highlighting the importance of centrosome regulation in cancers.[1] [2] [3]
Publication Abstract from PubMed
Centrioles are key microtubule polarity determinants. Centriole duplication is tightly controlled to prevent cells from developing multipolar spindles, a situation that promotes chromosomal instability. A conserved component in the duplication pathway is Plk4, a polo kinase family member that localizes to centrioles in M/G1. To limit centriole duplication, Plk4 levels are controlled through trans-autophosphorylation that primes ubiquitination. In contrast to Plks 1-3, Plk4 possesses a unique central region called the "cryptic polo box." Here, we present the crystal structure of this region at 2.3 A resolution. Surprisingly, the structure reveals two tandem homodimerized polo boxes, PB1-PB2, that form a unique winged architecture. The full PB1-PB2 cassette is required for binding the centriolar protein Asterless as well as robust centriole targeting. Thus, with its C-terminal polo box (PB3), Plk4 has a triple polo box architecture that facilitates oligomerization, targeting, and promotes trans-autophosphorylation, limiting centriole duplication to once per cell cycle.
The Structure of the Plk4 Cryptic Polo Box Reveals Two Tandem Polo Boxes Required for Centriole Duplication.,Slevin LK, Nye J, Pinkerton DC, Buster DW, Rogers GC, Slep KC Structure. 2012 Sep 18. pii: S0969-2126(12)00328-0. doi:, 10.1016/j.str.2012.08.025. PMID:23000383[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bettencourt-Dias M, Rodrigues-Martins A, Carpenter L, Riparbelli M, Lehmann L, Gatt MK, Carmo N, Balloux F, Callaini G, Glover DM. SAK/PLK4 is required for centriole duplication and flagella development. Curr Biol. 2005 Dec 20;15(24):2199-207. Epub 2005 Dec 1. PMID:16326102 doi:http://dx.doi.org/10.1016/j.cub.2005.11.042
- ↑ Rodrigues-Martins A, Riparbelli M, Callaini G, Glover DM, Bettencourt-Dias M. Revisiting the role of the mother centriole in centriole biogenesis. Science. 2007 May 18;316(5827):1046-50. Epub 2007 Apr 26. PMID:17463247 doi:http://dx.doi.org/10.1126/science.1142950
- ↑ Basto R, Brunk K, Vinadogrova T, Peel N, Franz A, Khodjakov A, Raff JW. Centrosome amplification can initiate tumorigenesis in flies. Cell. 2008 Jun 13;133(6):1032-42. doi: 10.1016/j.cell.2008.05.039. PMID:18555779 doi:http://dx.doi.org/10.1016/j.cell.2008.05.039
- ↑ Slevin LK, Nye J, Pinkerton DC, Buster DW, Rogers GC, Slep KC. The Structure of the Plk4 Cryptic Polo Box Reveals Two Tandem Polo Boxes Required for Centriole Duplication. Structure. 2012 Sep 18. pii: S0969-2126(12)00328-0. doi:, 10.1016/j.str.2012.08.025. PMID:23000383 doi:http://dx.doi.org/10.1016/j.str.2012.08.025
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