4n7v

From Proteopedia

(Difference between revisions)

Revision as of 08:43, 2 July 2014

Crystal structure of human Plk4 cryptic polo box (CPB) in complex with a Cep152 N-terminal fragment

Structural highlights

4n7v is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4n7z
Activity:	Polo kinase, with EC number 2.7.11.21
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[CE152_HUMAN] Seckel syndrome;Autosomal recessive primary microcephaly. The disease is caused by mutations affecting the gene represented in this entry. 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] [CE152_HUMAN] Necessary for centrosome duplication. Acts as a molecular scaffold facilitating the interaction of PLK4 and CENPJ, 2 molecules involved in centriole formation. Also plays a key role in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Overexpression of CEP152 can drive amplification of centrioles.^[7] ^[8] ^[9]

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
↑ Cizmecioglu O, Arnold M, Bahtz R, Settele F, Ehret L, Haselmann-Weiss U, Antony C, Hoffmann I. Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome. J Cell Biol. 2010 Nov 15;191(4):731-9. doi: 10.1083/jcb.201007107. Epub 2010 Nov , 8. PMID:21059844 doi:http://dx.doi.org/10.1083/jcb.201007107
↑ Dzhindzhev NS, Yu QD, Weiskopf K, Tzolovsky G, Cunha-Ferreira I, Riparbelli M, Rodrigues-Martins A, Bettencourt-Dias M, Callaini G, Glover DM. Asterless is a scaffold for the onset of centriole assembly. Nature. 2010 Oct 7;467(7316):714-8. doi: 10.1038/nature09445. Epub 2010 Sep 19. PMID:20852615 doi:http://dx.doi.org/10.1038/nature09445
↑ Kalay E, Yigit G, Aslan Y, Brown KE, Pohl E, Bicknell LS, Kayserili H, Li Y, Tuysuz B, Nurnberg G, Kiess W, Koegl M, Baessmann I, Buruk K, Toraman B, Kayipmaz S, Kul S, Ikbal M, Turner DJ, Taylor MS, Aerts J, Scott C, Milstein K, Dollfus H, Wieczorek D, Brunner HG, Hurles M, Jackson AP, Rauch A, Nurnberg P, Karaguzel A, Wollnik B. CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nat Genet. 2011 Jan;43(1):23-6. doi: 10.1038/ng.725. Epub 2010 Dec 5. PMID:21131973 doi:http://dx.doi.org/10.1038/ng.725

1 Structural highlights
2 Disease
3 Function
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4n7v"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==Crystal structure of human Plk4 cryptic polo box (CPB) in complex with a Cep152 N-terminal fragment==
+<StructureSection load='4n7v' size='340' side='right' caption='[[4n7v]], [[Resolution|resolution]] 2.76&Aring;' scene=''>
-The entry 4n7v is ON HOLD  until Paper Publication
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4n7v]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N7V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N7V FirstGlance]. <br>
-Authors: Park, S.-Y., Park, J.-E., Tian, L., Kim, T.-S., Yang, W., Lee, K.S.
+</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4n7z|4n7z]]</td></tr>
+<tr><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>
-Description:
+<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4n7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n7v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4n7v RCSB], [http://www.ebi.ac.uk/pdbsum/4n7v PDBsum]</span></td></tr>
+<table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/CE152_HUMAN CE152_HUMAN]] Seckel syndrome;Autosomal recessive primary microcephaly. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
+== Function ==
+[[http://www.uniprot.org/uniprot/PLK4_HUMAN 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.<ref>PMID:16326102</ref> <ref>PMID:16244668</ref> <ref>PMID:17681131</ref> <ref>PMID:18239451</ref> <ref>PMID:19164942</ref> <ref>PMID:21725316</ref>  [[http://www.uniprot.org/uniprot/CE152_HUMAN CE152_HUMAN]] Necessary for centrosome duplication. Acts as a molecular scaffold facilitating the interaction of PLK4 and CENPJ, 2 molecules involved in centriole formation. Also plays a key role in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Overexpression of CEP152 can drive amplification of centrioles.<ref>PMID:21059844</ref> <ref>PMID:20852615</ref> <ref>PMID:21131973</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Polo kinase]]
+[[Category: Kim, T S.]]
+[[Category: Lee, K S.]]
+[[Category: Park, J E.]]
+[[Category: Park, S Y.]]
+[[Category: Tian, L.]]
+[[Category: Yang, W.]]
+[[Category: Cell cycle]]
+[[Category: Centriole biogenesis]]
+[[Category: Centrosome]]
+[[Category: Cep152]]
+[[Category: D-rich motif]]
+[[Category: K/r crater]]

4n7v

From Proteopedia

Revision as of 08:43, 2 July 2014

Crystal structure of human Plk4 cryptic polo box (CPB) in complex with a Cep152 N-terminal fragment

Structural highlights

Disease

Function

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox