OCA at 11:00, 3 January 2024

OCA — Wed, 03 Jan 2024 11:00:55 GMT

←Older revision		Revision as of 11:00, 3 January 2024
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-	'''Unreleased structure'''

-	~~The entry~~ 7yq8 is ~~ON HOLD until 2025~~-02-05	+	==Cryo-EM structure of human topoisomerase II beta in complex with DNA and etoposide==
		+	<StructureSection load='7yq8' size='340' side='right'caption='[[7yq8]], [[Resolution\|resolution]] 3.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7yq8]] is a 6 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=7YQ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YQ8 FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3.9Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EVP:(5S,5AR,8AR,9R)-9-(4-HYDROXY-3,5-DIMETHOXYPHENYL)-8-OXO-5,5A,6,8,8A,9-HEXAHYDROFURO[3,4 6,7]NAPHTHO[2,3-D][1,3]DIOXOL-5-YL+4,6-O-[(1R)-ETHYLIDENE]-BETA-D-GLUCOPYRANOSIDE'>EVP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=7yq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yq8 OCA], [https://pdbe.org/7yq8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yq8 RCSB], [https://www.ebi.ac.uk/pdbsum/7yq8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yq8 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/TOP2B_HUMAN TOP2B_HUMAN] Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Indirectly involved in vitamin D-coupled transcription regulation via its association with the WINAC complex, a chromatin-remodeling complex recruited by vitamin D receptor (VDR), which is required for the ligand-bound VDR-mediated transrepression of the CYP27B1 gene.<ref>PMID:10684600</ref> <ref>PMID:12837248</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The function of the mitogen-activated protein kinase signaling pathway is required for the activation of immediate early genes (IEGs), including EGR1 and FOS, for cell growth and proliferation. Recent studies have identified topoisomerase II (TOP2) as one of the important regulators of the transcriptional activation of IEGs. However, the mechanism underlying transcriptional regulation involving TOP2 in IEG activation has remained unknown. Here, we demonstrate that ERK2, but not ERK1, is important for IEG transcriptional activation and report a critical ELK1 binding sequence for ERK2 function at the EGR1 gene. Our data indicate that both ERK1 and ERK2 extensively phosphorylate the C-terminal domain of TOP2B at mutual and distinctive residues. Although both ERK1 and ERK2 enhance the catalytic rate of TOP2B required to relax positive DNA supercoiling, ERK2 delays TOP2B catalysis of negative DNA supercoiling. In addition, ERK1 may relax DNA supercoiling by itself. ERK2 catalytic inhibition or knock-down interferes with transcription and deregulates TOP2B in IEGs. Furthermore, we present the first cryo-EM structure of the human cell-purified TOP2B and etoposide together with the EGR1 transcriptional start site (-30 to +20) that has the strongest affinity to TOP2B within -423 to +332. The structure shows TOP2B-mediated breakage and dramatic bending of the DNA. Transcription is activated by etoposide, while it is inhibited by ICRF193 at EGR1 and FOS, suggesting that TOP2B-mediated DNA break to favor transcriptional activation. Taken together, this study suggests that activated ERK2 phosphorylates TOP2B to regulate TOP2-DNA interactions and favor transcriptional activation in IEGs. We propose that TOP2B association, catalysis, and dissociation on its substrate DNA are important processes for regulating transcription and that ERK2-mediated TOP2B phosphorylation may be key for the catalysis and dissociation steps.

-	~~Authors~~:	+	ERK2-topoisomerase II regulatory axis is important for gene activation in immediate early genes.,Bunch H, Kim D, Naganuma M, Nakagawa R, Cong A, Jeong J, Ehara H, Vu H, Chang JH, Schellenberg MJ, Sekine SI Nat Commun. 2023 Dec 14;14(1):8341. doi: 10.1038/s41467-023-44089-y. PMID:38097570<ref>PMID:38097570</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 7yq8" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Bu H]]
		+	[[Category: Bunch H]]
		+	[[Category: Cong A]]
		+	[[Category: Ehara H]]
		+	[[Category: Jang J]]
		+	[[Category: Jeong J]]
		+	[[Category: Kim D]]
		+	[[Category: Naganuma M]]
		+	[[Category: Nakagawa R]]
		+	[[Category: Schellenberg MJ]]
		+	[[Category: Sekine S]]

OCA at 04:33, 11 October 2023

OCA — Wed, 11 Oct 2023 04:33:19 GMT

←Older revision		Revision as of 04:33, 11 October 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7yq8 is ON HOLD until ~~2024~~-11-05	+	The entry 7yq8 is ON HOLD until 2025-02-05

	Authors:		Authors:

OCA at 08:49, 2 August 2023

OCA — Wed, 02 Aug 2023 08:49:05 GMT

←Older revision		Revision as of 08:49, 2 August 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7yq8 is ON HOLD until ~~Paper Publication~~	+	The entry 7yq8 is ON HOLD until 2024-11-05

	Authors:		Authors:

OCA at 04:26, 28 September 2022

OCA — Wed, 28 Sep 2022 04:26:10 GMT

←Older revision		Revision as of 04:26, 28 September 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7yq8 is ON HOLD	+	The entry 7yq8 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7yq8" [edit=sysop:move=sysop]

OCA — Wed, 10 Aug 2022 03:49:54 GMT

Protected "7yq8" [edit=sysop:move=sysop]

←Older revision

Revision as of 03:49, 10 August 2022

OCA: New page: '''Unreleased structure''' The entry 7yq8 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 10 Aug 2022 03:49:53 GMT

New page: '''Unreleased structure''' The entry 7yq8 is ON HOLD Authors: Description: Category: Unreleased Structures

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