7x1n - Revision history

OCA at 17:46, 29 November 2023

OCA — Wed, 29 Nov 2023 17:46:55 GMT

←Older revision		Revision as of 17:46, 29 November 2023
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-	====	+	==Crystal structure of MEF2D-MRE complex==
-	<StructureSection load='7x1n' size='340' side='right'caption='[[7x1n]]' scene=''>	+	<StructureSection load='7x1n' size='340' side='right'caption='[[7x1n]], [[Resolution\|resolution]] 3.31Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7x1n]] is a 8 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=7X1N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7X1N FirstGlance]. <br>
-	</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=7x1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x1n OCA], [https://pdbe.org/7x1n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x1n RCSB], [https://www.ebi.ac.uk/pdbsum/7x1n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x1n ProSAT]</span></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]] 3.315Å</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=7x1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x1n OCA], [https://pdbe.org/7x1n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x1n RCSB], [https://www.ebi.ac.uk/pdbsum/7x1n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x1n ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q5IRN4_HUMAN Q5IRN4_HUMAN]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Recurrent MEF2D fusions with poor prognosis have been identified in B-cell precursor ALL (BCP-ALL). The molecular mechanisms underlying the pathogenic function of MEF2D fusions are poorly understood. Here, we show that MEF2D-HNRNPUL1 (MH) knock-in mice developed a progressive disease from impaired B-cell development at the pre-pro-B stage to pre-leukemia over 10 to 12 months. When cooperating with NRASG12D, MH drove an outbreak of BCP-ALL, with a more aggressive phenotype than the NRASG12D-induced leukemia. RNA-sequencing identified key networks involved in disease mechanisms. In chromatin immunoprecipitation-sequencing experiments, MH acquired increased chromatin-binding ability, mostly through MEF2D-responsive element (MRE) motifs in target genes, compared with wild-type MEF2D. Using X-ray crystallography, the MEF2D-MRE complex was characterized in atomic resolution, whereas disrupting the MH-DNA interaction alleviated the aberrant target gene expression and the B-cell differentiation arrest. The C-terminal moiety (HNRNPUL1 part) of MH was proven to contribute to the fusion protein's trans-regulatory activity, cofactor recruitment, and homodimerization. Furthermore, targeting MH-driven transactivation of the HDAC family by using the histone deacetylase inhibitor panobinostat in combination with chemotherapy improved the overall survival of MH/NRASG12D BCP-ALL mice. Altogether, these results not only highlight MH as an important driver in leukemogenesis but also provoke targeted intervention against BCP-ALL with MEF2D fusions.
		+
		+	Functional, structural, and molecular characterizations of the leukemogenic driver MEF2D-HNRNPUL1 fusion.,Zhang M, Zhang H, Li Z, Bai L, Wang Q, Li J, Jiang M, Xue Q, Cheng N, Zhang W, Mao D, Chen Z, Huang J, Meng G, Chen Z, Chen SJ Blood. 2022 Sep 22;140(12):1390-1407. doi: 10.1182/blood.2022016241. PMID:35544603<ref>PMID:35544603</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7x1n" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Myocyte enhancer factor 2\|Myocyte enhancer factor 2]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Z~~-disk~~]]	+	[[Category: Chen SJ]]
		+	[[Category: Chen Z]]
		+	[[Category: Meng G]]
		+	[[Category: Wang QQ]]
		+	[[Category: Zhang H]]
		+	[[Category: Zhang M]]

OCA at 08:00, 25 May 2022

OCA — Wed, 25 May 2022 08:00:37 GMT

←Older revision		Revision as of 08:00, 25 May 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7x1n ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7x1n' size='340' side='right'caption='[[7x1n]]' scene=''>
-	~~Authors~~: ~~Zhang, H~~.~~, Zhang, M~~.~~, Wang, Q~~.Q.~~, Chen, Z~~.~~, Chen, S~~.~~J., Meng, G~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure of MEF2D-MRE complex~~	+	</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=7x1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x1n OCA], [https://pdbe.org/7x1n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x1n RCSB], [https://www.ebi.ac.uk/pdbsum/7x1n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x1n ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[~~[Category~~: ~~Zhang, H]~~]	+	__TOC__
-	[~~[Category~~: ~~Wang, Q~~.Q]]	+	</StructureSection>
-	[~~[Category~~: ~~Zhang~~, ~~M]]~~	+	[[Category: Large Structures]]
-	[[~~Category~~: ~~Meng~~, G]]	+	[[Category: Z-disk]]
-	[[Category: ~~Chen, S.J~~]]	+
-	[[Category: ~~Chen,~~ Z]]	+

OCA at 05:03, 9 March 2022

OCA — Wed, 09 Mar 2022 05:03:58 GMT

←Older revision		Revision as of 05:03, 9 March 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7x1n is ON HOLD	+	The entry 7x1n is ON HOLD until Paper Publication

	Authors: Zhang, H., Zhang, M., Wang, Q.Q., Chen, Z., Chen, S.J., Meng, G.		Authors: Zhang, H., Zhang, M., Wang, Q.Q., Chen, Z., Chen, S.J., Meng, G.
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	Description: Crystal structure of MEF2D-MRE complex		Description: Crystal structure of MEF2D-MRE complex
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Zhang, M]]
	[[Category: Zhang, H]]		[[Category: Zhang, H]]
		+	[[Category: Wang, Q.Q]]
		+	[[Category: Zhang, M]]
	[[Category: Meng, G]]		[[Category: Meng, G]]
	[[Category: Chen, S.J]]		[[Category: Chen, S.J]]
	[[Category: Chen, Z]]		[[Category: Chen, Z]]
-	[[Category: Wang, Q.Q]]

OCA: Protected "7x1n" [edit=sysop:move=sysop]

OCA — Wed, 02 Mar 2022 05:16:57 GMT

Protected "7x1n" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:16, 2 March 2022

OCA: New page: '''Unreleased structure''' The entry 7x1n is ON HOLD Authors: Zhang, H., Zhang, M., Wang, Q.Q., Chen, Z., Chen, S.J., Meng, G. Description: Crystal structure of MEF2D-MRE complex [[Cat...

OCA — Wed, 02 Mar 2022 05:16:56 GMT

New page: '''Unreleased structure''' The entry 7x1n is ON HOLD Authors: Zhang, H., Zhang, M., Wang, Q.Q., Chen, Z., Chen, S.J., Meng, G. Description: Crystal structure of MEF2D-MRE complex [[Cat...

New page

'''Unreleased structure'''

The entry 7x1n is ON HOLD

Authors: Zhang, H., Zhang, M., Wang, Q.Q., Chen, Z., Chen, S.J., Meng, G.

Description: Crystal structure of MEF2D-MRE complex
[[Category: Unreleased Structures]]
[[Category: Zhang, M]]
[[Category: Zhang, H]]
[[Category: Meng, G]]
[[Category: Chen, S.J]]
[[Category: Chen, Z]]
[[Category: Wang, Q.Q]]