4iuf - Revision history

OCA at 11:59, 1 March 2024

OCA — Fri, 01 Mar 2024 11:59:53 GMT

←Older revision		Revision as of 11:59, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4iuf]] 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=4IUF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IUF FirstGlance]. <br>		<table><tr><td colspan='2'>[[4iuf]] 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=4IUF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IUF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XUA:2-SE-METHYL-2-SELENOADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>XUA</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]] 2.752Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XUA:2-SE-METHYL-2-SELENOADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>XUA</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=4iuf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iuf OCA], [https://pdbe.org/4iuf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iuf RCSB], [https://www.ebi.ac.uk/pdbsum/4iuf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iuf 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=4iuf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iuf OCA], [https://pdbe.org/4iuf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iuf RCSB], [https://www.ebi.ac.uk/pdbsum/4iuf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iuf ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/TADBP_HUMAN TADBP_HUMAN] DNA and RNA-binding protein which regulates transcription and splicing. Involved in the regulation of CFTR splicing. It promotes CFTR exon 9 skipping by binding to the UG repeated motifs in the polymorphic region near the 3'-splice site of this exon. The resulting aberrant splicing is associated with pathological features typical of cystic fibrosis. May also be involved in microRNA biogenesis, apoptosis and cell division. Can repress HIV-1 transcription by binding to the HIV-1 long terminal repeat. Stabilizes the low molecular weight neurofilament (NFL) mRNA through a direct interaction with the 3' UTR.<ref>PMID:17481916</ref> <ref>PMID:11285240</ref>		[https://www.uniprot.org/uniprot/TADBP_HUMAN TADBP_HUMAN] DNA and RNA-binding protein which regulates transcription and splicing. Involved in the regulation of CFTR splicing. It promotes CFTR exon 9 skipping by binding to the UG repeated motifs in the polymorphic region near the 3'-splice site of this exon. The resulting aberrant splicing is associated with pathological features typical of cystic fibrosis. May also be involved in microRNA biogenesis, apoptosis and cell division. Can repress HIV-1 transcription by binding to the HIV-1 long terminal repeat. Stabilizes the low molecular weight neurofilament (NFL) mRNA through a direct interaction with the 3' UTR.<ref>PMID:17481916</ref> <ref>PMID:11285240</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	TDP-43 is an important pathological protein that aggregates in the diseased neuronal cells and is linked to various neurodegenerative disorders. In normal cells, TDP-43 is primarily an RNA-binding protein; however, how the dimeric TDP-43 binds RNA via its two RNA recognition motifs, RRM1 and RRM2, is not clear. Here we report the crystal structure of human TDP-43 RRM1 in complex with a single-stranded DNA showing that RRM1 binds the nucleic acid extensively not only by the conserved beta-sheet residues but also by the loop residues. Mutational and biochemical assays further reveal that both RRMs in TDP-43 dimers participate in binding of UG-rich RNA or TG-rich DNA with RRM1 playing a dominant role and RRM2 playing a supporting role. Moreover, RRM1 of the amyotrophic lateral sclerosis-linked mutant D169G binds DNA as efficiently as the wild type; nevertheless, it is more resistant to thermal denaturation, suggesting that the resistance to degradation is likely linked to TDP-43 proteinopathies. Taken together all the data, we suggest a model showing that the two RRMs in each protomer of TDP-43 homodimer work together in RNA binding and thus the dimeric TDP-43 recognizes long clusters of UG-rich RNA to achieve high affinity and specificity.
-
-	The crystal structure of TDP-43 RRM1-DNA complex reveals the specific recognition for UG- and TG-rich nucleic acids.,Kuo PH, Chiang CH, Wang YT, Doudeva LG, Yuan HS Nucleic Acids Res. 2014 Apr;42(7):4712-22. doi: 10.1093/nar/gkt1407. Epub 2014, Jan 23. PMID:24464995<ref>PMID:24464995</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4iuf" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 21:11, 16 November 2022

OCA — Wed, 16 Nov 2022 21:11:41 GMT

←Older revision		Revision as of 21:11, 16 November 2022
Line 1:		Line 1:

	==Crystal Structure of Human TDP-43 RRM1 Domain in Complex with a Single-stranded DNA==		==Crystal Structure of Human TDP-43 RRM1 Domain in Complex with a Single-stranded DNA==
-	<StructureSection load='4iuf' size='340' side='right' caption='[[4iuf]], [[Resolution\|resolution]] 2.75Å' scene=''>	+	<StructureSection load='4iuf' size='340' side='right'caption='[[4iuf]], [[Resolution\|resolution]] 2.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4iuf]] 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=4IUF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4IUF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4iuf]] 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=4IUF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IUF FirstGlance]. <br>
-	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=XUA:2-SE-METHYL-2-SELENOADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>XUA</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XUA:2-SE-METHYL-2-SELENOADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>XUA</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TARDBP, TDP43 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=4iuf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iuf OCA], [https://pdbe.org/4iuf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iuf RCSB], [https://www.ebi.ac.uk/pdbsum/4iuf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iuf ProSAT]</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=4iuf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iuf OCA], [~~http~~://pdbe.org/4iuf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4iuf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4iuf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4iuf ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/TADBP_HUMAN TADBP_HUMAN]] Defects in TARDBP are the cause of amyotrophic lateral sclerosis type 10 (ALS10) [MIM:[~~http~~://omim.org/entry/612069 612069]]. ALS is a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of ALS is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.<ref>PMID:20740007</ref> <ref>PMID:18288693</ref> <ref>PMID:18438952</ref> <ref>PMID:18396105</ref> <ref>PMID:18372902</ref> <ref>PMID:18309045</ref> <ref>PMID:19350673</ref> <ref>PMID:19224587</ref> <ref>PMID:19655382</ref> <ref>PMID:19695877</ref> <ref>PMID:21220647</ref> <ref>PMID:21418058</ref> <ref>PMID:22456481</ref>	+	[https://www.uniprot.org/uniprot/TADBP_HUMAN TADBP_HUMAN] Defects in TARDBP are the cause of amyotrophic lateral sclerosis type 10 (ALS10) [MIM:[https://omim.org/entry/612069 612069]. ALS is a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of ALS is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.<ref>PMID:20740007</ref> <ref>PMID:18288693</ref> <ref>PMID:18438952</ref> <ref>PMID:18396105</ref> <ref>PMID:18372902</ref> <ref>PMID:18309045</ref> <ref>PMID:19350673</ref> <ref>PMID:19224587</ref> <ref>PMID:19655382</ref> <ref>PMID:19695877</ref> <ref>PMID:21220647</ref> <ref>PMID:21418058</ref> <ref>PMID:22456481</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/TADBP_HUMAN TADBP_HUMAN]] DNA and RNA-binding protein which regulates transcription and splicing. Involved in the regulation of CFTR splicing. It promotes CFTR exon 9 skipping by binding to the UG repeated motifs in the polymorphic region near the 3'-splice site of this exon. The resulting aberrant splicing is associated with pathological features typical of cystic fibrosis. May also be involved in microRNA biogenesis, apoptosis and cell division. Can repress HIV-1 transcription by binding to the HIV-1 long terminal repeat. Stabilizes the low molecular weight neurofilament (NFL) mRNA through a direct interaction with the 3' UTR.<ref>PMID:17481916</ref> <ref>PMID:11285240</ref>	+	[https://www.uniprot.org/uniprot/TADBP_HUMAN TADBP_HUMAN] DNA and RNA-binding protein which regulates transcription and splicing. Involved in the regulation of CFTR splicing. It promotes CFTR exon 9 skipping by binding to the UG repeated motifs in the polymorphic region near the 3'-splice site of this exon. The resulting aberrant splicing is associated with pathological features typical of cystic fibrosis. May also be involved in microRNA biogenesis, apoptosis and cell division. Can repress HIV-1 transcription by binding to the HIV-1 long terminal repeat. Stabilizes the low molecular weight neurofilament (NFL) mRNA through a direct interaction with the 3' UTR.<ref>PMID:17481916</ref> <ref>PMID:11285240</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Doudeva, L G~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Kuo, P H~~]]	+	[[Category: Doudeva LG]]
-	[[Category: ~~Wang, Y T~~]]	+	[[Category: Kuo PH]]
-	[[Category: ~~Yang, W Z~~]]	+	[[Category: Wang YT]]
-	[[Category: ~~Yuan, H S~~]]	+	[[Category: Yang WZ]]
-	[[Category: ~~Dna binding]]~~	+	[[Category: Yuan HS]]
-	~~[[Category: Protein-dna complex]]~~	+
-	~~[[Category: Rna binding]]~~	+
-	~~[[Category: Rna recognition motif]]~~	+
-	~~[[Category: Splicing factor]]~~	+
-	~~[[Category: Transcription regulator-dna complex~~]]	+

OCA at 18:58, 11 August 2016

OCA — Thu, 11 Aug 2016 18:58:12 GMT

←Older revision		Revision as of 18:58, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of Human TDP-43 RRM1 Domain in Complex with a Single-stranded DNA==		==Crystal Structure of Human TDP-43 RRM1 Domain in Complex with a Single-stranded DNA==
	<StructureSection load='4iuf' size='340' side='right' caption='[[4iuf]], [[Resolution\|resolution]] 2.75Å' scene=''>		<StructureSection load='4iuf' size='340' side='right' caption='[[4iuf]], [[Resolution\|resolution]] 2.75Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=XUA:2-SE-METHYL-2-SELENOADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>XUA</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=XUA:2-SE-METHYL-2-SELENOADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>XUA</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TARDBP, TDP43 ([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">TARDBP, TDP43 ([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=4iuf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iuf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iuf RCSB], [http://www.ebi.ac.uk/pdbsum/4iuf 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=4iuf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iuf OCA], [http://pdbe.org/4iuf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iuf RCSB], [http://www.ebi.ac.uk/pdbsum/4iuf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iuf ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	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 4iuf" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:17, 20 January 2015

OCA — Tue, 20 Jan 2015 09:17:11 GMT

←Older revision		Revision as of 09:17, 20 January 2015
Line 24:		Line 24:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Doudeva, L G.]]	+	[[Category: Doudeva, L G]]
-	[[Category: Kuo, P H.]]	+	[[Category: Kuo, P H]]
-	[[Category: Wang, Y T.]]	+	[[Category: Wang, Y T]]
-	[[Category: Yang, W Z.]]	+	[[Category: Yang, W Z]]
-	[[Category: Yuan, H S.]]	+	[[Category: Yuan, H S]]
	[[Category: Dna binding]]		[[Category: Dna binding]]
	[[Category: Protein-dna complex]]		[[Category: Protein-dna complex]]

OCA at 05:46, 8 October 2014

OCA — Wed, 08 Oct 2014 05:46:21 GMT

←Older revision		Revision as of 05:46, 8 October 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4iuf\| PDB=4iuf \| SCENE= }}~~	+	==Crystal Structure of Human TDP-43 RRM1 Domain in Complex with a Single-stranded DNA==
-	===Crystal Structure of Human TDP-43 RRM1 Domain in Complex with a Single-stranded DNA===	+	<StructureSection load='4iuf' size='340' side='right' caption='[[4iuf]], [[Resolution\|resolution]] 2.75Å' scene=''>
-		+	== Structural highlights ==
-	==Disease==	+	<table><tr><td colspan='2'>[[4iuf]] 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=4IUF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IUF FirstGlance]. <br>
		+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=XUA:2-SE-METHYL-2-SELENOADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>XUA</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TARDBP, TDP43 ([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=4iuf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iuf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iuf RCSB], [http://www.ebi.ac.uk/pdbsum/4iuf PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/TADBP_HUMAN TADBP_HUMAN]] Defects in TARDBP are the cause of amyotrophic lateral sclerosis type 10 (ALS10) [MIM:[http://omim.org/entry/612069 612069]]. ALS is a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of ALS is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.<ref>PMID:20740007</ref> <ref>PMID:18288693</ref> <ref>PMID:18438952</ref> <ref>PMID:18396105</ref> <ref>PMID:18372902</ref> <ref>PMID:18309045</ref> <ref>PMID:19350673</ref> <ref>PMID:19224587</ref> <ref>PMID:19655382</ref> <ref>PMID:19695877</ref> <ref>PMID:21220647</ref> <ref>PMID:21418058</ref> <ref>PMID:22456481</ref>		[[http://www.uniprot.org/uniprot/TADBP_HUMAN TADBP_HUMAN]] Defects in TARDBP are the cause of amyotrophic lateral sclerosis type 10 (ALS10) [MIM:[http://omim.org/entry/612069 612069]]. ALS is a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of ALS is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.<ref>PMID:20740007</ref> <ref>PMID:18288693</ref> <ref>PMID:18438952</ref> <ref>PMID:18396105</ref> <ref>PMID:18372902</ref> <ref>PMID:18309045</ref> <ref>PMID:19350673</ref> <ref>PMID:19224587</ref> <ref>PMID:19655382</ref> <ref>PMID:19695877</ref> <ref>PMID:21220647</ref> <ref>PMID:21418058</ref> <ref>PMID:22456481</ref>
-		+	== Function ==
-	==Function==	+
	[[http://www.uniprot.org/uniprot/TADBP_HUMAN TADBP_HUMAN]] DNA and RNA-binding protein which regulates transcription and splicing. Involved in the regulation of CFTR splicing. It promotes CFTR exon 9 skipping by binding to the UG repeated motifs in the polymorphic region near the 3'-splice site of this exon. The resulting aberrant splicing is associated with pathological features typical of cystic fibrosis. May also be involved in microRNA biogenesis, apoptosis and cell division. Can repress HIV-1 transcription by binding to the HIV-1 long terminal repeat. Stabilizes the low molecular weight neurofilament (NFL) mRNA through a direct interaction with the 3' UTR.<ref>PMID:17481916</ref> <ref>PMID:11285240</ref>		[[http://www.uniprot.org/uniprot/TADBP_HUMAN TADBP_HUMAN]] DNA and RNA-binding protein which regulates transcription and splicing. Involved in the regulation of CFTR splicing. It promotes CFTR exon 9 skipping by binding to the UG repeated motifs in the polymorphic region near the 3'-splice site of this exon. The resulting aberrant splicing is associated with pathological features typical of cystic fibrosis. May also be involved in microRNA biogenesis, apoptosis and cell division. Can repress HIV-1 transcription by binding to the HIV-1 long terminal repeat. Stabilizes the low molecular weight neurofilament (NFL) mRNA through a direct interaction with the 3' UTR.<ref>PMID:17481916</ref> <ref>PMID:11285240</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	TDP-43 is an important pathological protein that aggregates in the diseased neuronal cells and is linked to various neurodegenerative disorders. In normal cells, TDP-43 is primarily an RNA-binding protein; however, how the dimeric TDP-43 binds RNA via its two RNA recognition motifs, RRM1 and RRM2, is not clear. Here we report the crystal structure of human TDP-43 RRM1 in complex with a single-stranded DNA showing that RRM1 binds the nucleic acid extensively not only by the conserved beta-sheet residues but also by the loop residues. Mutational and biochemical assays further reveal that both RRMs in TDP-43 dimers participate in binding of UG-rich RNA or TG-rich DNA with RRM1 playing a dominant role and RRM2 playing a supporting role. Moreover, RRM1 of the amyotrophic lateral sclerosis-linked mutant D169G binds DNA as efficiently as the wild type; nevertheless, it is more resistant to thermal denaturation, suggesting that the resistance to degradation is likely linked to TDP-43 proteinopathies. Taken together all the data, we suggest a model showing that the two RRMs in each protomer of TDP-43 homodimer work together in RNA binding and thus the dimeric TDP-43 recognizes long clusters of UG-rich RNA to achieve high affinity and specificity.

-	~~==About this Structure==~~	+	The crystal structure of TDP-43 RRM1-DNA complex reveals the specific recognition for UG- and TG-rich nucleic acids.,Kuo PH, Chiang CH, Wang YT, Doudeva LG, Yuan HS Nucleic Acids Res. 2014 Apr;42(7):4712-22. doi: 10.1093/nar/gkt1407. Epub 2014, Jan 23. PMID:24464995<ref>PMID:24464995</ref>
-	~~[[4iuf]] is a 2 chain~~ structure. ~~Full crystallographic information is available from [http~~:~~//oca~~.~~weizmann~~.~~ac.il~~/~~oca-bin~~/~~ocashort?id=4IUF OCA]~~.	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
	[[Category: Doudeva, L G.]]		[[Category: Doudeva, L G.]]
	[[Category: Kuo, P H.]]		[[Category: Kuo, P H.]]

OCA at 07:45, 29 January 2014

OCA — Wed, 29 Jan 2014 07:45:36 GMT

←Older revision		Revision as of 07:45, 29 January 2014
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-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4iuf\| PDB=4iuf \| SCENE= }}
		+	===Crystal Structure of Human TDP-43 RRM1 Domain in Complex with a Single-stranded DNA===

-	~~The~~ entry ~~4iuf~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/TADBP_HUMAN TADBP_HUMAN]] Defects in TARDBP are the cause of amyotrophic lateral sclerosis type 10 (ALS10) [MIM:[http://omim.org/entry/612069 612069]]. ALS is a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of ALS is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.<ref>PMID:20740007</ref> <ref>PMID:18288693</ref> <ref>PMID:18438952</ref> <ref>PMID:18396105</ref> <ref>PMID:18372902</ref> <ref>PMID:18309045</ref> <ref>PMID:19350673</ref> <ref>PMID:19224587</ref> <ref>PMID:19655382</ref> <ref>PMID:19695877</ref> <ref>PMID:21220647</ref> <ref>PMID:21418058</ref> <ref>PMID:22456481</ref>

-	~~Authors~~: ~~Kuo, P~~.H.~~, Doudeva, L~~.G.~~, Wang, Y~~.T., ~~Yang, W~~.Z.~~, Yuan, H.S~~.	+	==Function==
		+	[[http://www.uniprot.org/uniprot/TADBP_HUMAN TADBP_HUMAN]] DNA and RNA-binding protein which regulates transcription and splicing. Involved in the regulation of CFTR splicing. It promotes CFTR exon 9 skipping by binding to the UG repeated motifs in the polymorphic region near the 3'-splice site of this exon. The resulting aberrant splicing is associated with pathological features typical of cystic fibrosis. May also be involved in microRNA biogenesis, apoptosis and cell division. Can repress HIV-1 transcription by binding to the HIV-1 long terminal repeat. Stabilizes the low molecular weight neurofilament (NFL) mRNA through a direct interaction with the 3' UTR.<ref>PMID:17481916</ref> <ref>PMID:11285240</ref>

-	~~Description: Crystal~~ Structure ~~of Human TDP-43 RRM1 Domain in Complex with~~ a ~~Single~~-~~stranded DNA~~	+	==About this Structure==
		+	[[4iuf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IUF OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: Doudeva, L G.]]
		+	[[Category: Kuo, P H.]]
		+	[[Category: Wang, Y T.]]
		+	[[Category: Yang, W Z.]]
		+	[[Category: Yuan, H S.]]
		+	[[Category: Dna binding]]
		+	[[Category: Protein-dna complex]]
		+	[[Category: Rna binding]]
		+	[[Category: Rna recognition motif]]
		+	[[Category: Splicing factor]]
		+	[[Category: Transcription regulator-dna complex]]

OCA at 06:48, 16 May 2013

OCA — Thu, 16 May 2013 06:48:07 GMT

←Older revision		Revision as of 06:48, 16 May 2013
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4iuf is ON HOLD	+	The entry 4iuf is ON HOLD until Paper Publication

	Authors: Kuo, P.H., Doudeva, L.G., Wang, Y.T., Yang, W.Z., Yuan, H.S.		Authors: Kuo, P.H., Doudeva, L.G., Wang, Y.T., Yang, W.Z., Yuan, H.S.

-	Description: Crystal Structure ~~Analysis~~ of Human TDP-43 RRM1 Domain ~~and~~ Single-stranded ~~10mer~~ DNA ~~(GTTGAGCGTT) Complex~~	+	Description: Crystal Structure of Human TDP-43 RRM1 Domain in Complex with a Single-stranded DNA

OCA at 12:28, 6 February 2013

OCA — Wed, 06 Feb 2013 12:28:42 GMT

←Older revision		Revision as of 12:28, 6 February 2013
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	The entry 4iuf is ON HOLD		The entry 4iuf is ON HOLD

-	Authors: Kuo, P. H., Doudeva, L.G., Wang, Y. T., Yang, W. Z., Yuan, H.S.	+	Authors: Kuo, P.H., Doudeva, L.G., Wang, Y.T., Yang, W.Z., Yuan, H.S.

-	Description: Crystal Structure Analysis of Human TDP-43 RRM1 Domain and Single-stranded 10mer DNA (GTTGAGCGTT) Complex ~~"HOLD FOR PUBLICATION" (CASP Target)~~	+	Description: Crystal Structure Analysis of Human TDP-43 RRM1 Domain and Single-stranded 10mer DNA (GTTGAGCGTT) Complex

OCA: Protected "4iuf" [edit=sysop:move=sysop]

OCA — Wed, 30 Jan 2013 12:05:03 GMT

Protected "4iuf" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:05, 30 January 2013

OCA: New page: '''Unreleased structure''' The entry 4iuf is ON HOLD Authors: Kuo, P. H., Doudeva, L.G., Wang, Y. T., Yang, W. Z., Yuan, H.S. Description: Crystal Structure Analysis of Human TDP-43 RR...

OCA — Wed, 30 Jan 2013 12:05:02 GMT

New page: '''Unreleased structure''' The entry 4iuf is ON HOLD Authors: Kuo, P. H., Doudeva, L.G., Wang, Y. T., Yang, W. Z., Yuan, H.S. Description: Crystal Structure Analysis of Human TDP-43 RR...

New page

'''Unreleased structure'''

The entry 4iuf is ON HOLD

Authors: Kuo, P. H., Doudeva, L.G., Wang, Y. T., Yang, W. Z., Yuan, H.S.

Description: Crystal Structure Analysis of Human TDP-43 RRM1 Domain and Single-stranded 10mer DNA (GTTGAGCGTT) Complex "HOLD FOR PUBLICATION" (CASP Target)