6n45 - Revision history

OCA at 06:44, 11 October 2023

OCA — Wed, 11 Oct 2023 06:44:47 GMT

←Older revision		Revision as of 06:44, 11 October 2023
Line 3:		Line 3:
	<StructureSection load='6n45' size='340' side='right'caption='[[6n45]], [[Resolution\|resolution]] 2.64Å' scene=''>		<StructureSection load='6n45' size='340' side='right'caption='[[6n45]], [[Resolution\|resolution]] 2.64Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6n45]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N45 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6N45 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6n45]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N45 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N45 FirstGlance]. <br>
-	</td></tr><tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~DCAF1~~, ~~KIAA0800, RIP, VPRBP (~~[~~http://www~~.~~ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info~~&~~srchmode=5&id=9606 HUMAN])~~</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]] 2.64Å</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=6n45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n45 OCA], [~~http~~://pdbe.org/6n45 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6n45 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6n45 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6n45 ProSAT]</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=6n45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n45 OCA], [https://pdbe.org/6n45 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n45 RCSB], [https://www.ebi.ac.uk/pdbsum/6n45 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n45 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== 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>	+	[https://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> [https://www.uniprot.org/uniprot/DCAF1_HUMAN DCAF1_HUMAN] Acts both as a substrate recognition component of E3 ubiquitin-protein ligase complexes and as an atypical serine/threonine-protein kinase, playing key roles in various processes such as cell cycle, telomerase regulation and histone modification. Probable substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, named CUL4A-RBX1-DDB1-DCAF1/VPRBP complex, which mediates ubiquitination and proteasome-dependent degradation of proteins such as NF2. Involved in the turnover of methylated proteins: recognizes and binds methylated proteins via its chromo domain, leading to ubiquitination of target proteins by the RBX1-DDB1-DCAF1/VPRBP complex (PubMed:23063525). The CUL4A-RBX1-DDB1-DCAF1/VPRBP complex is also involved in B-cell development: DCAF1 is recruited by RAG1 to ubiquitinate proteins, leading to limit error-prone repair during V(D)J recombination. Also part of the EDVP complex, an E3 ligase complex that mediates ubiquitination of proteins such as TERT, leading to TERT degradation and telomerase inhibition (PubMed:23362280). Also acts as an atypical serine/threonine-protein kinase that specifically mediates phosphorylation of 'Thr-120' of histone H2A (H2AT120ph) in a nucleosomal context, thereby repressing transcription. H2AT120ph is present in the regulatory region of many tumor suppresor genes, down-regulates their transcription and is present at high level in a number of tumors (PubMed:24140421). Involved in JNK-mediated apoptosis during cell competition process via its interaction with LLGL1 and LLGL2 (PubMed:20644714).<ref>PMID:16964240</ref> <ref>PMID:17609381</ref> <ref>PMID:17630831</ref> <ref>PMID:18332868</ref> <ref>PMID:18524771</ref> <ref>PMID:18606781</ref> <ref>PMID:19287380</ref> <ref>PMID:20644714</ref> <ref>PMID:22184063</ref> <ref>PMID:23063525</ref> <ref>PMID:23362280</ref> <ref>PMID:24140421</ref> (Microbial infection) In case of infection by HIV-1 virus, it is recruited by HIV-1 Vpr in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to arrest the cell cycle in G2 phase, and also to protect the viral protein from proteasomal degradation by another E3 ubiquitin ligase. The HIV-1 Vpr protein hijacks the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex to promote ubiquitination and degradation of proteins such as TERT and ZIP/ZGPAT.<ref>PMID:17314515</ref> <ref>PMID:17559673</ref> <ref>PMID:17609381</ref> <ref>PMID:17620334</ref> <ref>PMID:17626091</ref> <ref>PMID:17630831</ref> <ref>PMID:18524771</ref> <ref>PMID:24116224</ref> (Microbial infection) In case of infection by HIV-2 virus, it is recruited by HIV-2 Vpx in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to enhanced efficiency of macrophage infection and promotion of the replication of cognate primate lentiviruses in cells of monocyte/macrophage lineage.<ref>PMID:17314515</ref> <ref>PMID:18464893</ref> <ref>PMID:19264781</ref> <ref>PMID:19923175</ref> <ref>PMID:24336198</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Lee~~, K S~~]]	+	[[Category: Lee KS]]
-	[[Category: Meng, L]]	+	[[Category: Meng L]]
-	[[Category: Park, J E]]	+	[[Category: Park J-E]]
-	[[Category: Zhang, L]]	+	[[Category: Zhang L]]
-	~~[[Category: Cell cycle]]~~	+
-	~~[[Category: Centriole duplication]]~~	+
-	~~[[Category: Pcm organization]]~~	+
-	~~[[Category: Phase separation]]~~	+
-	~~[[Category: Polo-like kinase 4]]~~	+
-	~~[[Category: Protein phosphorylation~~]]	+

OCA at 17:35, 20 November 2019

OCA — Wed, 20 Nov 2019 17:35:44 GMT

←Older revision		Revision as of 17:35, 20 November 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6n45 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of the cryptic polo box domain of human activated Plk4 variant 1==
		+	<StructureSection load='6n45' size='340' side='right'caption='[[6n45]], [[Resolution\|resolution]] 2.64Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6n45]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N45 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N45 FirstGlance]. <br>
		+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DCAF1, KIAA0800, RIP, VPRBP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6n45 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n45 OCA], [http://pdbe.org/6n45 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n45 RCSB], [http://www.ebi.ac.uk/pdbsum/6n45 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n45 ProSAT]</span></td></tr>
		+	</table>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Tight control of centriole duplication is critical for normal chromosome segregation and the maintenance of genomic stability. Polo-like kinase 4 (Plk4) is a key regulator of centriole biogenesis. How Plk4 dynamically promotes its symmetry-breaking relocalization and achieves its procentriole-assembly state remains unknown. Here we show that Plk4 is a unique kinase that utilizes its autophosphorylated noncatalytic cryptic polo-box (CPB) to phase separate and generate a nanoscale spherical condensate. Analyses of the crystal structure of a phospho-mimicking, condensation-proficient CPB mutant reveal that a disordered loop at the CPB PB2-tip region is critically required for Plk4 to generate condensates and induce procentriole assembly. CPB phosphorylation also promotes Plk4's dissociation from the Cep152 tether while binding to downstream STIL, thus allowing Plk4 condensate to serve as an assembling body for centriole biogenesis. This study uncovers the mechanism underlying Plk4 activation and may offer strategies for anti-Plk4 intervention against genomic instability and cancer.

-	~~Authors~~:	+	Phase separation of Polo-like kinase 4 by autoactivation and clustering drives centriole biogenesis.,Park JE, Zhang L, Bang JK, Andresson T, DiMaio F, Lee KS Nat Commun. 2019 Oct 31;10(1):4959. doi: 10.1038/s41467-019-12619-2. PMID:31672968<ref>PMID:31672968</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6n45" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
		+	[[Category: Lee, K S]]
		+	[[Category: Meng, L]]
		+	[[Category: Park, J E]]
		+	[[Category: Zhang, L]]
		+	[[Category: Cell cycle]]
		+	[[Category: Centriole duplication]]
		+	[[Category: Pcm organization]]
		+	[[Category: Phase separation]]
		+	[[Category: Polo-like kinase 4]]
		+	[[Category: Protein phosphorylation]]

OCA at 06:24, 30 January 2019

OCA — Wed, 30 Jan 2019 06:24:59 GMT

←Older revision		Revision as of 06:24, 30 January 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6n45 is ON HOLD	+	The entry 6n45 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6n45" [edit=sysop:move=sysop]

OCA — Sun, 02 Dec 2018 19:14:30 GMT

Protected "6n45" [edit=sysop:move=sysop]

←Older revision

Revision as of 19:14, 2 December 2018

OCA: New page: '''Unreleased structure''' The entry 6n45 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Sun, 02 Dec 2018 19:14:29 GMT

New page: '''Unreleased structure''' The entry 6n45 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6n45 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]