5mr7 - Revision history

OCA at 17:46, 8 November 2023

2023-11-08T17:46:47Z

←Older revision		Revision as of 17:46, 8 November 2023
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	==Crystal structure of the DBD domain of human Grhl2==		==Crystal structure of the DBD domain of human Grhl2==
-	<StructureSection load='5mr7' size='340' side='right' caption='[[5mr7]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='5mr7' size='340' side='right'caption='[[5mr7]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mr7]] 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=5MR7 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5MR7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mr7]] 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=5MR7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MR7 FirstGlance]. <br>
-	</td></tr><tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~GRHL2~~, ~~BOM, TFCP2L3 (~~[~~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]] 2.5Å</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=5mr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mr7 OCA], [~~http~~://pdbe.org/5mr7 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5mr7 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5mr7 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5mr7 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=5mr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mr7 OCA], [https://pdbe.org/5mr7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mr7 RCSB], [https://www.ebi.ac.uk/pdbsum/5mr7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mr7 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/GRHL2_HUMAN GRHL2_HUMAN]] Autosomal dominant non-syndromic sensorineural deafness type DFNA. 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.	+	[https://www.uniprot.org/uniprot/GRHL2_HUMAN GRHL2_HUMAN] Autosomal dominant non-syndromic sensorineural deafness type DFNA. 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 ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/GRHL2_HUMAN GRHL2_HUMAN]] Transcription factor playing an important role in primary neurulation and in epithelial development (PubMed:25152456). Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes (By similarity). During embryogenesis, plays unique and cooperative roles with GRHL3 in establishing distinct zones of primary neurulation. Essential for closure 3 (rostral end of the forebrain), functions cooperatively with GRHL3 in closure 2 (forebrain/midbrain boundary) and posterior neuropore closure (By similarity). Regulates epithelial morphogenesis acting as a target gene-associated transcriptional activator of apical junctional complex components. Up-regulates of CLDN3 and CLDN4, as well as of RAB25, which increases the CLDN4 protein and its localization at tight junctions (By similarity). Comprises an essential component of the transcriptional machinery that establishes appropriate expression levels of CLDN4 and CDH1 in different types of epithelia. Exhibits functional redundancy with GRHL3 in epidermal morphogenetic events and epidermal wound repair (By similarity). In lung, forms a regulatory loop with NKX2-1 that coordinates lung epithelial cell morphogenesis and differentiation (By similarity). In keratinocytes, plays a role in telomerase activation during cellular proliferation, regulates TERT expression by binding to TERT promoter region and inhibiting DNA methylation at the 5'-CpG island, possibly by interfering with DNMT1 enzyme activity (PubMed:19015635, PubMed:20938050). In addition, impairs keratinocyte differentiation and epidermal function by inhibiting the expression of genes clustered at the epidermal differentiation complex (EDC) as well as GRHL1 and GRHL3 through epigenetic mechanisms (PubMed:23254293).[UniProtKB:Q8K5C0]<ref>PMID:19015635</ref> <ref>PMID:20938050</ref> <ref>PMID:20978075</ref> <ref>PMID:23254293</ref> <ref>PMID:25152456</ref> <ref>PMID:12175488</ref>	+	[https://www.uniprot.org/uniprot/GRHL2_HUMAN GRHL2_HUMAN] Transcription factor playing an important role in primary neurulation and in epithelial development (PubMed:25152456). Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes (By similarity). During embryogenesis, plays unique and cooperative roles with GRHL3 in establishing distinct zones of primary neurulation. Essential for closure 3 (rostral end of the forebrain), functions cooperatively with GRHL3 in closure 2 (forebrain/midbrain boundary) and posterior neuropore closure (By similarity). Regulates epithelial morphogenesis acting as a target gene-associated transcriptional activator of apical junctional complex components. Up-regulates of CLDN3 and CLDN4, as well as of RAB25, which increases the CLDN4 protein and its localization at tight junctions (By similarity). Comprises an essential component of the transcriptional machinery that establishes appropriate expression levels of CLDN4 and CDH1 in different types of epithelia. Exhibits functional redundancy with GRHL3 in epidermal morphogenetic events and epidermal wound repair (By similarity). In lung, forms a regulatory loop with NKX2-1 that coordinates lung epithelial cell morphogenesis and differentiation (By similarity). In keratinocytes, plays a role in telomerase activation during cellular proliferation, regulates TERT expression by binding to TERT promoter region and inhibiting DNA methylation at the 5'-CpG island, possibly by interfering with DNMT1 enzyme activity (PubMed:19015635, PubMed:20938050). In addition, impairs keratinocyte differentiation and epidermal function by inhibiting the expression of genes clustered at the epidermal differentiation complex (EDC) as well as GRHL1 and GRHL3 through epigenetic mechanisms (PubMed:23254293).[UniProtKB:Q8K5C0]<ref>PMID:19015635</ref> <ref>PMID:20938050</ref> <ref>PMID:20978075</ref> <ref>PMID:23254293</ref> <ref>PMID:25152456</ref> <ref>PMID:12175488</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: Heinemann, U]]	+	[[Category: Large Structures]]
-	[[Category: Ming, Q]]	+	[[Category: Heinemann U]]
-	[[Category: Roske, Y]]	+	[[Category: Ming Q]]
-	[[Category: Schuetz, A]]	+	[[Category: Roske Y]]
-	~~[[Category: Dna-binding domain]]~~	+	[[Category: Schuetz A]]
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Transcription factor~~]]	+

OCA at 06:48, 14 March 2018

2018-03-14T06:48:41Z

←Older revision		Revision as of 06:48, 14 March 2018
Line 3:		Line 3:
	<StructureSection load='5mr7' size='340' side='right' caption='[[5mr7]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='5mr7' size='340' side='right' caption='[[5mr7]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mr7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MR7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MR7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mr7]] 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=5MR7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MR7 FirstGlance]. <br>
-	</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=5mr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mr7 OCA], [http://pdbe.org/5mr7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mr7 RCSB], [http://www.ebi.ac.uk/pdbsum/5mr7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mr7 ProSAT]</span></td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GRHL2, BOM, TFCP2L3 ([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=5mr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mr7 OCA], [http://pdbe.org/5mr7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mr7 RCSB], [http://www.ebi.ac.uk/pdbsum/5mr7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mr7 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Heinemann, U]]		[[Category: Heinemann, U]]
	[[Category: Ming, Q]]		[[Category: Ming, Q]]

OCA at 06:47, 17 January 2018

2018-01-17T06:47:50Z

←Older revision		Revision as of 06:47, 17 January 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The entry ~~5mr7~~ is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of the DBD domain of human Grhl2==
		+	<StructureSection load='5mr7' size='340' side='right' caption='[[5mr7]], [[Resolution\|resolution]] 2.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5mr7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MR7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MR7 FirstGlance]. <br>
		+	</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=5mr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mr7 OCA], [http://pdbe.org/5mr7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mr7 RCSB], [http://www.ebi.ac.uk/pdbsum/5mr7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mr7 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/GRHL2_HUMAN GRHL2_HUMAN]] Autosomal dominant non-syndromic sensorineural deafness type DFNA. 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/GRHL2_HUMAN GRHL2_HUMAN]] Transcription factor playing an important role in primary neurulation and in epithelial development (PubMed:25152456). Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes (By similarity). During embryogenesis, plays unique and cooperative roles with GRHL3 in establishing distinct zones of primary neurulation. Essential for closure 3 (rostral end of the forebrain), functions cooperatively with GRHL3 in closure 2 (forebrain/midbrain boundary) and posterior neuropore closure (By similarity). Regulates epithelial morphogenesis acting as a target gene-associated transcriptional activator of apical junctional complex components. Up-regulates of CLDN3 and CLDN4, as well as of RAB25, which increases the CLDN4 protein and its localization at tight junctions (By similarity). Comprises an essential component of the transcriptional machinery that establishes appropriate expression levels of CLDN4 and CDH1 in different types of epithelia. Exhibits functional redundancy with GRHL3 in epidermal morphogenetic events and epidermal wound repair (By similarity). In lung, forms a regulatory loop with NKX2-1 that coordinates lung epithelial cell morphogenesis and differentiation (By similarity). In keratinocytes, plays a role in telomerase activation during cellular proliferation, regulates TERT expression by binding to TERT promoter region and inhibiting DNA methylation at the 5'-CpG island, possibly by interfering with DNMT1 enzyme activity (PubMed:19015635, PubMed:20938050). In addition, impairs keratinocyte differentiation and epidermal function by inhibiting the expression of genes clustered at the epidermal differentiation complex (EDC) as well as GRHL1 and GRHL3 through epigenetic mechanisms (PubMed:23254293).[UniProtKB:Q8K5C0]<ref>PMID:19015635</ref> <ref>PMID:20938050</ref> <ref>PMID:20978075</ref> <ref>PMID:23254293</ref> <ref>PMID:25152456</ref> <ref>PMID:12175488</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Grainyhead (Grh)/CP2 transcription factors are highly conserved in multicellular organisms as key regulators of epithelial differentiation, organ development and skin barrier formation. In addition, they have been implicated as being tumor suppressors in a variety of human cancers. Despite their physiological importance, little is known about their structure and DNA binding mode. Here, we report the first structural study of mammalian Grh/CP2 factors. Crystal structures of the DNA-binding domains of grainyhead-like (Grhl) 1 and Grhl2 reveal a closely similar conformation with immunoglobulin-like core. Both share a common fold with the tumor suppressor p53, but differ in important structural features. The Grhl1 DNA-binding domain binds duplex DNA containing the consensus recognition element in a dimeric arrangement, supporting parsimonious target-sequence selection through two conserved arginine residues. We elucidate the molecular basis of a cancer-related mutation in Grhl1 involving one of these arginines, which completely abrogates DNA binding in biochemical assays and transcriptional activation of a reporter gene in a human cell line. Thus, our studies establish the structural basis of DNA target-site recognition by Grh transcription factors and reveal how tumor-associated mutations inactivate Grhl proteins. They may serve as points of departure for the structure-based development of Grh/CP2 inhibitors for therapeutic applications.

-	~~Authors~~:	+	Structural basis of gene regulation by the Grainyhead/CP2 transcription factor family.,Ming Q, Roske Y, Schuetz A, Walentin K, Ibraimi I, Schmidt-Ott KM, Heinemann U Nucleic Acids Res. 2018 Jan 4. pii: 4788346. doi: 10.1093/nar/gkx1299. PMID:29309642<ref>PMID:29309642</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5mr7" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Heinemann, U]]
		+	[[Category: Ming, Q]]
		+	[[Category: Roske, Y]]
		+	[[Category: Schuetz, A]]
		+	[[Category: Dna-binding domain]]
		+	[[Category: Transcription]]
		+	[[Category: Transcription factor]]

OCA: Protected "5mr7" [edit=sysop:move=sysop]

2017-01-02T13:55:29Z

Protected "5mr7" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:55, 2 January 2017

OCA: New page: '''Unreleased structure''' The entry 5mr7 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

2017-01-02T13:55:28Z

New page: '''Unreleased structure''' The entry 5mr7 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5mr7 is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]