3cbb - Revision history

OCA at 09:34, 21 February 2024

2024-02-21T09:34:14Z

← Older revision		Revision as of 09:34, 21 February 2024
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	<StructureSection load='3cbb' size='340' side='right'caption='[[3cbb]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3cbb' size='340' side='right'caption='[[3cbb]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3cbb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CBB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CBB FirstGlance]. <br>		<table><tr><td colspan='2'>[[3cbb]] is a 4 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=3CBB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CBB FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>~~</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]] 2Å</td></tr>
	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~HNF4A, HNF4, NR2A1, TCF14 ([https~~:/~~/www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=3cbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cbb OCA], [https://pdbe.org/3cbb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cbb RCSB], [https://www.ebi.ac.uk/pdbsum/3cbb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cbb 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=3cbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cbb OCA], [https://pdbe.org/3cbb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cbb RCSB], [https://www.ebi.ac.uk/pdbsum/3cbb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cbb ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/HNF4A_HUMAN HNF4A_HUMAN]] Defects in HNF4A are the cause of maturity-onset diabetes of the young type 1 (MODY1) [MIM:[https://omim.org/entry/125850 125850]]; also symbolized MODY-1. MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:9313765</ref> <ref>PMID:9243109</ref> <ref>PMID:9449683</ref>		[https://www.uniprot.org/uniprot/HNF4A_HUMAN HNF4A_HUMAN] Defects in HNF4A are the cause of maturity-onset diabetes of the young type 1 (MODY1) [MIM:[https://omim.org/entry/125850 125850]; also symbolized MODY-1. MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:9313765</ref> <ref>PMID:9243109</ref> <ref>PMID:9449683</ref>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/HNF4A_HUMAN HNF4A_HUMAN]] Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.		[https://www.uniprot.org/uniprot/HNF4A_HUMAN HNF4A_HUMAN] Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3cbb ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3cbb ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	HNF4alpha (hepatocyte nuclear factor 4alpha) plays an essential role in the development and function of vertebrate organs, including hepatocytes and pancreatic beta-cells by regulating expression of multiple genes involved in organ development, nutrient transport, and diverse metabolic pathways. As such, HNF4alpha is a culprit gene product for a monogenic and dominantly inherited form of diabetes, known as maturity onset diabetes of the young (MODY). As a unique member of the nuclear receptor superfamily, HNF4alpha recognizes target genes containing two hexanucleotide direct repeat DNA-response elements separated by one base pair (DR1) by exclusively forming a cooperative homodimer. We describe here the 2.0 angstroms crystal structure of human HNF4alpha DNA binding domain in complex with a high affinity promoter element of another MODY gene, HNF1alpha, which reveals the molecular basis of unique target gene selection/recognition, DNA binding cooperativity, and dysfunction caused by diabetes-causing mutations. The predicted effects of MODY mutations have been tested by a set of biochemical and functional studies, which show that, in contrast to other MODY gene products, the subtle disruption of HNF4alpha molecular function can cause significant effects in afflicted MODY patients.

	Structural basis of natural promoter recognition by a unique nuclear receptor, HNF4alpha. Diabetes gene product.,Lu P, Rha GB, Melikishvili M, Wu G, Adkins BC, Fried MG, Chi YI J Biol Chem. 2008 Nov 28;283(48):33685-97. Epub 2008 Oct 1. PMID:18829458<ref>PMID:18829458</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 3cbb" style="background-color:#fffaf0;"></div>~~
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Adkins~~, B C~~]]		[[Category: Adkins BC]]
	[[Category: Chi~~, Y I~~]]		[[Category: Chi YI]]
	[[Category: Fried~~, M G~~]]		[[Category: Fried MG]]
	[[Category: Lu, P]]		[[Category: Lu P]]
	[[Category: Melikishvili, M]]		[[Category: Melikishvili M]]
	[[Category: Rha~~, G B]]~~		[[Category: Rha GB]]
	~~[[Category: Diabetes]]~~
	~~[[Category: Protein-dna complex]]~~
	~~[[Category: Transcription-dna complex]]~~
	~~[[Category: Zinc finger~~]]

OCA at 07:49, 27 January 2022

2022-01-27T07:49:50Z

← Older revision		Revision as of 07:49, 27 January 2022
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	==Crystal Structure of Hepatocyte Nuclear Factor 4alpha in complex with DNA: Diabetes Gene Product==		==Crystal Structure of Hepatocyte Nuclear Factor 4alpha in complex with DNA: Diabetes Gene Product==
	<StructureSection load='3cbb' size='340' side='right' caption='[[3cbb]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3cbb' size='340' side='right'caption='[[3cbb]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3cbb]] is a 4 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=3CBB OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3CBB FirstGlance]. <br>		<table><tr><td colspan='2'>[[3cbb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CBB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CBB FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HNF4A, HNF4, NR2A1, TCF14 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HNF4A, HNF4, NR2A1, TCF14 ([https://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=3cbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cbb OCA], [~~http~~://pdbe.org/3cbb PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3cbb RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3cbb PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3cbb 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=3cbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cbb OCA], [https://pdbe.org/3cbb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cbb RCSB], [https://www.ebi.ac.uk/pdbsum/3cbb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cbb ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/HNF4A_HUMAN HNF4A_HUMAN]] Defects in HNF4A are the cause of maturity-onset diabetes of the young type 1 (MODY1) [MIM:[~~http~~://omim.org/entry/125850 125850]]; also symbolized MODY-1. MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:9313765</ref> <ref>PMID:9243109</ref> <ref>PMID:9449683</ref>		[[https://www.uniprot.org/uniprot/HNF4A_HUMAN HNF4A_HUMAN]] Defects in HNF4A are the cause of maturity-onset diabetes of the young type 1 (MODY1) [MIM:[https://omim.org/entry/125850 125850]]; also symbolized MODY-1. MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:9313765</ref> <ref>PMID:9243109</ref> <ref>PMID:9449683</ref>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/HNF4A_HUMAN HNF4A_HUMAN]] Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.		[[https://www.uniprot.org/uniprot/HNF4A_HUMAN HNF4A_HUMAN]] Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cb/3cbb_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cb/3cbb_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Adkins, B C]]		[[Category: Adkins, B C]]
	[[Category: Chi, Y I]]		[[Category: Chi, Y I]]

OCA at 08:22, 25 October 2017

2017-10-25T08:22:08Z

← Older revision		Revision as of 08:22, 25 October 2017
Line 1:		Line 1:

	==Crystal Structure of Hepatocyte Nuclear Factor 4alpha in complex with DNA: Diabetes Gene Product==		==Crystal Structure of Hepatocyte Nuclear Factor 4alpha in complex with DNA: Diabetes Gene Product==
	<StructureSection load='3cbb' size='340' side='right' caption='[[3cbb]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3cbb' size='340' side='right' caption='[[3cbb]], [[Resolution\|resolution]] 2.00Å' scene=''>
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	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HNF4A, HNF4, NR2A1, TCF14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HNF4A, HNF4, NR2A1, TCF14 ([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=3cbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cbb OCA], [http://pdbe.org/3cbb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cbb RCSB], [http://www.ebi.ac.uk/pdbsum/3cbb PDBsum]</span></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=3cbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cbb OCA], [http://pdbe.org/3cbb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cbb RCSB], [http://www.ebi.ac.uk/pdbsum/3cbb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3cbb ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==

OCA at 16:02, 8 February 2016

2016-02-08T16:02:57Z

← Older revision		Revision as of 16:02, 8 February 2016
Line 2:		Line 2:
	<StructureSection load='3cbb' size='340' side='right' caption='[[3cbb]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3cbb' size='340' side='right' caption='[[3cbb]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3cbb]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CBB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CBB FirstGlance]. <br>		<table><tr><td colspan='2'>[[3cbb]] is a 4 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=3CBB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CBB FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HNF4A, HNF4, NR2A1, TCF14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HNF4A, HNF4, NR2A1, TCF14 ([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=3cbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cbb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cbb RCSB], [http://www.ebi.ac.uk/pdbsum/3cbb PDBsum]</span></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=3cbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cbb OCA], [http://pdbe.org/3cbb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cbb RCSB], [http://www.ebi.ac.uk/pdbsum/3cbb PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 19:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3cbb ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 3cbb" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Adkins, B C]]		[[Category: Adkins, B C]]
	[[Category: Chi, Y I]]		[[Category: Chi, Y I]]

OCA at 07:42, 20 January 2015

2015-01-20T07:42:58Z

← Older revision		Revision as of 07:42, 20 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3cbb]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CBB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CBB FirstGlance]. <br>		<table><tr><td colspan='2'>[[3cbb]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CBB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CBB FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HNF4A, HNF4, NR2A1, TCF14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HNF4A, HNF4, NR2A1, TCF14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
	<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=3cbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cbb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cbb RCSB], [http://www.ebi.ac.uk/pdbsum/3cbb PDBsum]</span></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=3cbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cbb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cbb RCSB], [http://www.ebi.ac.uk/pdbsum/3cbb PDBsum]</span></td></tr>
	<table>		</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/HNF4A_HUMAN HNF4A_HUMAN]] Defects in HNF4A are the cause of maturity-onset diabetes of the young type 1 (MODY1) [MIM:[http://omim.org/entry/125850 125850]]; also symbolized MODY-1. MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:9313765</ref> <ref>PMID:9243109</ref> <ref>PMID:9449683</ref>		[[http://www.uniprot.org/uniprot/HNF4A_HUMAN HNF4A_HUMAN]] Defects in HNF4A are the cause of maturity-onset diabetes of the young type 1 (MODY1) [MIM:[http://omim.org/entry/125850 125850]]; also symbolized MODY-1. MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:9313765</ref> <ref>PMID:9243109</ref> <ref>PMID:9449683</ref>
Line 34:		Line 34:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Adkins, B C.]]		[[Category: Adkins, B C]]
	[[Category: Chi, Y I.]]		[[Category: Chi, Y I]]
	[[Category: Fried, M G.]]		[[Category: Fried, M G]]
	[[Category: Lu, P.]]		[[Category: Lu, P]]
	[[Category: Melikishvili, M.]]		[[Category: Melikishvili, M]]
	[[Category: Rha, G B.]]		[[Category: Rha, G B]]
	[[Category: Diabetes]]		[[Category: Diabetes]]
	[[Category: Protein-dna complex]]		[[Category: Protein-dna complex]]
	[[Category: Transcription-dna complex]]		[[Category: Transcription-dna complex]]
	[[Category: Zinc finger]]		[[Category: Zinc finger]]

OCA at 20:47, 2 October 2014

2014-10-02T20:47:56Z

← Older revision		Revision as of 20:47, 2 October 2014
Line 1:		Line 1:
	~~{{STRUCTURE_3cbb\| PDB=3cbb \| SCENE= }}~~		==Crystal Structure of Hepatocyte Nuclear Factor 4alpha in complex with DNA: Diabetes Gene Product==
	===Crystal Structure of Hepatocyte Nuclear Factor 4alpha in complex with DNA: Diabetes Gene Product===		<StructureSection load='3cbb' size='340' side='right' caption='[[3cbb]], [[Resolution\|resolution]] 2.00Å' scene=''>
	~~{{ABSTRACT_PUBMED_18829458}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[3cbb]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CBB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CBB FirstGlance]. <br>
	==Disease==		</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
	[[http://www.uniprot.org/uniprot/HNF4A_HUMAN HNF4A_HUMAN]] Defects in HNF4A are the cause of maturity-onset diabetes of the young type 1 (MODY1) [MIM:[http://omim.org/entry/125850 125850]]; also symbolized MODY-1. MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:9313765</ref><ref>PMID:9243109</ref><ref>PMID:9449683</ref>		<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HNF4A, HNF4, NR2A1, TCF14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
			<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=3cbb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cbb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cbb RCSB], [http://www.ebi.ac.uk/pdbsum/3cbb PDBsum]</span></td></tr>
	==Function==		<table>
			== Disease ==
			[[http://www.uniprot.org/uniprot/HNF4A_HUMAN HNF4A_HUMAN]] Defects in HNF4A are the cause of maturity-onset diabetes of the young type 1 (MODY1) [MIM:[http://omim.org/entry/125850 125850]]; also symbolized MODY-1. MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:9313765</ref> <ref>PMID:9243109</ref> <ref>PMID:9449683</ref>
			== Function ==
	[[http://www.uniprot.org/uniprot/HNF4A_HUMAN HNF4A_HUMAN]] Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.		[[http://www.uniprot.org/uniprot/HNF4A_HUMAN HNF4A_HUMAN]] Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.
			== Evolutionary Conservation ==
			[[Image:Consurf_key_small.gif\|200px\|right]]
			Check<jmol>
			<jmolCheckbox>
			<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cb/3cbb_consurf.spt"</scriptWhenChecked>
			<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
			<text>to colour the structure by Evolutionary Conservation</text>
			</jmolCheckbox>
			</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
			<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			HNF4alpha (hepatocyte nuclear factor 4alpha) plays an essential role in the development and function of vertebrate organs, including hepatocytes and pancreatic beta-cells by regulating expression of multiple genes involved in organ development, nutrient transport, and diverse metabolic pathways. As such, HNF4alpha is a culprit gene product for a monogenic and dominantly inherited form of diabetes, known as maturity onset diabetes of the young (MODY). As a unique member of the nuclear receptor superfamily, HNF4alpha recognizes target genes containing two hexanucleotide direct repeat DNA-response elements separated by one base pair (DR1) by exclusively forming a cooperative homodimer. We describe here the 2.0 angstroms crystal structure of human HNF4alpha DNA binding domain in complex with a high affinity promoter element of another MODY gene, HNF1alpha, which reveals the molecular basis of unique target gene selection/recognition, DNA binding cooperativity, and dysfunction caused by diabetes-causing mutations. The predicted effects of MODY mutations have been tested by a set of biochemical and functional studies, which show that, in contrast to other MODY gene products, the subtle disruption of HNF4alpha molecular function can cause significant effects in afflicted MODY patients.

	~~==About this Structure==~~		Structural basis of natural promoter recognition by a unique nuclear receptor, HNF4alpha. Diabetes gene product.,Lu P, Rha GB, Melikishvili M, Wu G, Adkins BC, Fried MG, Chi YI J Biol Chem. 2008 Nov 28;283(48):33685-97. Epub 2008 Oct 1. PMID:18829458<ref>PMID:18829458</ref>
	~~[[3cbb]] is~~ a ~~4 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http~~:~~//oca~~.~~weizmann~~.~~ac.il~~/~~oca-bin/ocashort?id=3CBB OCA].~~

	==~~Reference~~==		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~<ref group="xtra">PMID:018829458</ref>~~<references ~~group="xtra"~~/><~~references~~/>		</div>
			== References ==
			<references/>
			__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Adkins, B C.]]		[[Category: Adkins, B C.]]

OCA at 18:11, 24 March 2013

2013-03-24T18:11:41Z

← Older revision		Revision as of 18:11, 24 March 2013
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	~~[[Image:3cbb.png\|left\|200px]]~~

	{{STRUCTURE_3cbb\| PDB=3cbb \| SCENE= }}		{{STRUCTURE_3cbb\| PDB=3cbb \| SCENE= }}
			===Crystal Structure of Hepatocyte Nuclear Factor 4alpha in complex with DNA: Diabetes Gene Product===
			{{ABSTRACT_PUBMED_18829458}}

	===~~Crystal Structure~~ of ~~Hepatocyte Nuclear Factor 4alpha~~ in ~~complex with DNA~~: ~~Diabetes Gene Product===~~		==Disease==
			[[http://www.uniprot.org/uniprot/HNF4A_HUMAN HNF4A_HUMAN]] Defects in HNF4A are the cause of maturity-onset diabetes of the young type 1 (MODY1) [MIM:[http://omim.org/entry/125850 125850]]; also symbolized MODY-1. MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:9313765</ref><ref>PMID:9243109</ref><ref>PMID:9449683</ref>

	~~{{ABSTRACT_PUBMED_18829458}}~~		==Function==
			[[http://www.uniprot.org/uniprot/HNF4A_HUMAN HNF4A_HUMAN]] Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.

	==About this Structure==		==About this Structure==
Line 11:		Line 13:

	==Reference==		==Reference==
	<ref group="xtra">PMID:018829458</ref><references group="xtra"/>		<ref group="xtra">PMID:018829458</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Adkins, B C.]]		[[Category: Adkins, B C.]]

OCA: Protected "3cbb" [edit=sysop:move=sysop]

2013-01-07T20:37:46Z

Protected "3cbb" [edit=sysop:move=sysop]

← Older revision	Revision as of 20:37, 7 January 2013
(No difference)

OCA at 20:37, 7 January 2013

2013-01-07T20:37:43Z

← Older revision		Revision as of 20:37, 7 January 2013
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	~~{{Seed}}~~
	[[Image:3cbb.png\|left\|200px]]		[[Image:3cbb.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_3cbb", creates the "Structure Box" on the page.~~
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display.~~
	~~-->~~
	{{STRUCTURE_3cbb\| PDB=3cbb \| SCENE= }}		{{STRUCTURE_3cbb\| PDB=3cbb \| SCENE= }}

	===Crystal Structure of Hepatocyte Nuclear Factor 4alpha in complex with DNA: Diabetes Gene Product===		===Crystal Structure of Hepatocyte Nuclear Factor 4alpha in complex with DNA: Diabetes Gene Product===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_18829458}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 18829458 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_18829458}}		{{ABSTRACT_PUBMED_18829458}}

	==About this Structure==		==About this Structure==
	~~3CBB~~ is a 4 ~~chains~~ structure ~~of sequences~~ from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CBB OCA].		[[3cbb]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CBB OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~18829458~~</ref><references group="xtra"/>		<ref group="xtra">PMID:018829458</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Adkins, B C.]]		[[Category: Adkins, B C.]]
Line 33:		Line 21:
	[[Category: Diabetes]]		[[Category: Diabetes]]
	[[Category: Protein-dna complex]]		[[Category: Protein-dna complex]]
	[[Category: Transcription/dna complex]]		[[Category: Transcription-dna complex]]
	[[Category: Zinc finger]]		[[Category: Zinc finger]]

	~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Dec 24 07:32:53 2009''~~

OCA at 05:32, 24 December 2009

2009-12-24T05:32:54Z

← Older revision		Revision as of 05:32, 24 December 2009
Line 12:		Line 12:
	===Crystal Structure of Hepatocyte Nuclear Factor 4alpha in complex with DNA: Diabetes Gene Product===		===Crystal Structure of Hepatocyte Nuclear Factor 4alpha in complex with DNA: Diabetes Gene Product===


			<!--
			The line below this paragraph, {{ABSTRACT_PUBMED_18829458}}, adds the Publication Abstract to the page
			(as it appears on PubMed at http://www.pubmed.gov), where 18829458 is the PubMed ID number.
			-->
			{{ABSTRACT_PUBMED_18829458}}

	==About this Structure==		==About this Structure==
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	[[Category: Zinc finger]]		[[Category: Zinc finger]]

	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed~~ Dec ~~23 09~~:04:44 2009''		''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Dec 24 07:32:53 2009''