This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4yyp

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 13:31, 4 May 2017

Crystal structure of human PLK4-PB3 in complex with STIL-CC

Structural highlights

4yyp is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2n15
Activity:	Polo kinase, with EC number 2.7.11.21
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[STIL_HUMAN] Precursor T-cell acute lymphoblastic leukemia;Autosomal recessive primary microcephaly. A chromosomal aberration involving STIL may be a cause of some T-cell acute lymphoblastic leukemias (T-ALL). A deletion at 1p32 between STIL and TAL1 genes leads to STIL/TAL1 fusion mRNA with STIL exon 1 slicing to TAL1 exon 3. As both STIL exon 1 and TAL1 exon 3 are 5'-untranslated exons, STIL/TAL1 fusion mRNA predicts a full length TAL1 protein under the control of the STIL promoter, leading to inappropriate TAL1 expression. In childhood T-cell malignancies (T-ALL), a type of defect such as STIL/TAL1 fusion is associated with a good prognosis. In cultured lymphocytes from healthy adults, STIL/TAL1 fusion mRNA may be detected after 7 days of culture. The disease is caused by mutations affecting the gene represented in this entry.

Function

[PLK4_HUMAN] Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] [STIL_HUMAN] Immediate-early gene. Plays an important role in embryonic development as well as in cellular growth and proliferation; its long-term silencing affects cell survival and cell cycle distribution as well as decreases CDK1 activity correlated with reduced phosphorylation of CDK1. Plays a role as a positive regulator of the sonic hedgehog pathway, acting downstream of PTCH1.^[7] ^[8]

Publication Abstract from PubMed

Polo-like kinases (PLK) are eukaryotic regulators of cell cycle progression, mitosis and cytokinesis; PLK4 is a master regulator of centriole duplication. Here, we demonstrate that the SCL/TAL1 interrupting locus (STIL) protein interacts via its coiled-coil region (STIL-CC) with PLK4 in vivo. STIL-CC is the first identified interaction partner of Polo-box 3 (PB3) of PLK4 and also uses a secondary interaction site in the PLK4 L1 region. Structure determination of free PLK4-PB3 and its STIL-CC complex via NMR and crystallography reveals a novel mode of Polo-box-peptide interaction mimicking coiled-coil formation. In vivo analysis of structure-guided STIL mutants reveals distinct binding modes to PLK4-PB3 and L1, as well as interplay of STIL oligomerization with PLK4 binding. We suggest that the STIL-CC/PLK4 interaction mediates PLK4 activation as well as stabilization of centriolar PLK4 and plays a key role in centriole duplication.

STIL binding to Polo-box 3 of PLK4 regulates centriole duplication.,Arquint C, Gabryjonczyk AM, Imseng S, Bohm R, Sauer E, Hiller S, Nigg EA, Maier T Elife. 2015 Jul 18;4. doi: 10.7554/eLife.07888. PMID:26188084^[9]

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
↑ Habedanck R, Stierhof YD, Wilkinson CJ, Nigg EA. The Polo kinase Plk4 functions in centriole duplication. Nat Cell Biol. 2005 Nov;7(11):1140-6. PMID:16244668 doi:http://dx.doi.org/10.1038/ncb1320
↑ Kleylein-Sohn J, Westendorf J, Le Clech M, Habedanck R, Stierhof YD, Nigg EA. Plk4-induced centriole biogenesis in human cells. Dev Cell. 2007 Aug;13(2):190-202. PMID:17681131 doi:http://dx.doi.org/10.1016/j.devcel.2007.07.002
↑ Bonni S, Ganuelas ML, Petrinac S, Hudson JW. Human Plk4 phosphorylates Cdc25C. Cell Cycle. 2008 Feb 15;7(4):545-7. Epub 2007 Nov 25. PMID:18239451
↑ Petrinac S, Ganuelas ML, Bonni S, Nantais J, Hudson JW. Polo-like kinase 4 phosphorylates Chk2. Cell Cycle. 2009 Jan 15;8(2):327-9. PMID:19164942
↑ Puklowski A, Homsi Y, Keller D, May M, Chauhan S, Kossatz U, Grunwald V, Kubicka S, Pich A, Manns MP, Hoffmann I, Gonczy P, Malek NP. The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication. Nat Cell Biol. 2011 Jul 3;13(8):1004-9. doi: 10.1038/ncb2282. PMID:21725316 doi:http://dx.doi.org/10.1038/ncb2282
↑ Campaner S, Kaldis P, Izraeli S, Kirsch IR. Sil phosphorylation in a Pin1 binding domain affects the duration of the spindle checkpoint. Mol Cell Biol. 2005 Aug;25(15):6660-72. PMID:16024801 doi:http://dx.doi.org/10.1128/MCB.25.15.6660-6672.2005
↑ Izraeli S, Colaizzo-Anas T, Bertness VL, Mani K, Aplan PD, Kirsch IR. Expression of the SIL gene is correlated with growth induction and cellular proliferation. Cell Growth Differ. 1997 Nov;8(11):1171-9. PMID:9372240
↑ Arquint C, Gabryjonczyk AM, Imseng S, Bohm R, Sauer E, Hiller S, Nigg EA, Maier T. STIL binding to Polo-box 3 of PLK4 regulates centriole duplication. Elife. 2015 Jul 18;4. doi: 10.7554/eLife.07888. PMID:26188084 doi:http://dx.doi.org/10.7554/eLife.07888

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/4yyp"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human PLK4-PB3 in complex with STIL-CC==
 <StructureSection load='4yyp' size='340' side='right' caption='[[4yyp]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2n15|2n15]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yyp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yyp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yyp RCSB], [http://www.ebi.ac.uk/pdbsum/4yyp PDBsum]</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=4yyp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yyp OCA], [http://pdbe.org/4yyp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yyp RCSB], [http://www.ebi.ac.uk/pdbsum/4yyp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yyp ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4yyp" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4yyp

From Proteopedia

Revision as of 13:31, 4 May 2017

Crystal structure of human PLK4-PB3 in complex with STIL-CC

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox