4nk7

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Crystal Structure of the D. melanogaster Plk4 cryptic polo box (CPB)

Structural highlights

4nk7 is a 1 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.233Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Plk4 family kinases control centriole assembly. Plk4s target mother centrioles through an interaction between their cryptic polo box (CPB) and acidic regions in the centriolar receptors SPD-2/Cep192 and/or Asterless/Cep152. Here, we report a crystal structure for the CPB of C. elegans ZYG-1, which forms a Z-shaped dimer containing an intermolecular beta sheet with an extended basic surface patch. Biochemical and in vivo analysis revealed that electrostatic interactions dock the ZYG-1 CPB basic patch onto the SPD-2-derived acidic region to promote ZYG-1 targeting and new centriole assembly. Analysis of a different crystal form of the Drosophila Plk4 (DmPlk4) CPB suggests that it also forms a Z-shaped dimer. Comparison of the ZYG-1 and DmPlk4 CPBs revealed structural changes in the ZYG-1 CPB that confer selectivity for binding SPD-2 over Asterless-derived acidic regions. Overall, our findings suggest a conserved mechanism for centriolar docking of Plk4 homologs that initiate daughter centriole assembly.

Structure of the C. elegans ZYG-1 Cryptic Polo Box Suggests a Conserved Mechanism for Centriolar Docking of Plk4 Kinases.,Shimanovskaya E, Viscardi V, Lesigang J, Lettman MM, Qiao R, Svergun DI, Round A, Oegema K, Dong G Structure. 2014 Aug 5;22(8):1090-104. doi: 10.1016/j.str.2014.05.009. Epub 2014, Jun 26. PMID:24980795^[4]

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

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
↑ Shimanovskaya E, Viscardi V, Lesigang J, Lettman MM, Qiao R, Svergun DI, Round A, Oegema K, Dong G. Structure of the C. elegans ZYG-1 Cryptic Polo Box Suggests a Conserved Mechanism for Centriolar Docking of Plk4 Kinases. Structure. 2014 Aug 5;22(8):1090-104. doi: 10.1016/j.str.2014.05.009. Epub 2014, Jun 26. PMID:24980795 doi:http://dx.doi.org/10.1016/j.str.2014.05.009