4bs2 - Revision history

OCA at 10:08, 14 June 2023

2023-06-14T10:08:25Z

←Older revision		Revision as of 10:08, 14 June 2023
Line 7:		Line 7:
	</table>		</table>
	== Disease ==		== Disease ==
-	[[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>	+	[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 ==
-	[[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 encodes an alternative-splicing regulator with tandem RNA-recognition motifs (RRMs). The protein regulates cystic fibrosis transmembrane regulator (CFTR) exon 9 splicing through binding to long UG-rich RNA sequences and is found in cytoplasmic inclusions of several neurodegenerative diseases. We solved the solution structure of the TDP-43 RRMs in complex with UG-rich RNA. Ten nucleotides are bound by both RRMs, and six are recognized sequence specifically. Among these, a central G interacts with both RRMs and stabilizes a new tandem RRM arrangement. Mutations that eliminate recognition of this key nucleotide or crucial inter-RRM interactions disrupt RNA binding and TDP-43-dependent splicing regulation. In contrast, point mutations that affect base-specific recognition in either RRM have weaker effects. Our findings reveal not only how TDP-43 recognizes UG repeats but also how RNA binding-dependent inter-RRM interactions are crucial for TDP-43 function.
		+
		+	Molecular basis of UG-rich RNA recognition by the human splicing factor TDP-43.,Lukavsky PJ, Daujotyte D, Tollervey JR, Ule J, Stuani C, Buratti E, Baralle FE, Damberger FF, Allain FH Nat Struct Mol Biol. 2013 Nov 17. doi: 10.1038/nsmb.2698. PMID:24240615<ref>PMID:24240615</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 4bs2" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 17:03, 7 September 2022

2022-09-07T17:03:35Z

←Older revision		Revision as of 17:03, 7 September 2022
Line 1:		Line 1:

	==NMR structure of human TDP-43 tandem RRMs in complex with UG-rich RNA==		==NMR structure of human TDP-43 tandem RRMs in complex with UG-rich RNA==
-	<StructureSection load='4bs2' size='340' side='right'caption='[[4bs2~~]], [[NMR_Ensembles_of_Models \| 20 NMR models~~]]' scene=''>	+	<StructureSection load='4bs2' size='340' side='right'caption='[[4bs2]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4bs2]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BS2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4BS2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4bs2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BS2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BS2 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=4bs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bs2 OCA], [~~http~~://pdbe.org/4bs2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4bs2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4bs2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4bs2 ProSAT]</span></td></tr>	+	</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=4bs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bs2 OCA], [https://pdbe.org/4bs2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bs2 RCSB], [https://www.ebi.ac.uk/pdbsum/4bs2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bs2 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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	TDP-43 encodes an alternative-splicing regulator with tandem RNA-recognition motifs (RRMs). The protein regulates cystic fibrosis transmembrane regulator (CFTR) exon 9 splicing through binding to long UG-rich RNA sequences and is found in cytoplasmic inclusions of several neurodegenerative diseases. We solved the solution structure of the TDP-43 RRMs in complex with UG-rich RNA. Ten nucleotides are bound by both RRMs, and six are recognized sequence specifically. Among these, a central G interacts with both RRMs and stabilizes a new tandem RRM arrangement. Mutations that eliminate recognition of this key nucleotide or crucial inter-RRM interactions disrupt RNA binding and TDP-43-dependent splicing regulation. In contrast, point mutations that affect base-specific recognition in either RRM have weaker effects. Our findings reveal not only how TDP-43 recognizes UG repeats but also how RNA binding-dependent inter-RRM interactions are crucial for TDP-43 function.	+
-		+
-	Molecular basis of UG-rich RNA recognition by the human splicing factor TDP-43.,Lukavsky PJ, Daujotyte D, Tollervey JR, Ule J, Stuani C, Buratti E, Baralle FE, Damberger FF, Allain FH Nat Struct Mol Biol. 2013 Nov 17. doi: 10.1038/nsmb.2698. PMID:24240615<ref>PMID:24240615</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4bs2" style="background-color:#fffaf0;"></div>~~	+
-		+
-	~~==See Also==~~	+
-	*[[Tdp-43\|Tdp-43]]	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Allain~~, F H.T~~]]	+	[[Category: Allain FHT]]
-	[[Category: Baralle~~, F E~~]]	+	[[Category: Baralle FE]]
-	[[Category: Buratti, E]]	+	[[Category: Buratti E]]
-	[[Category: Damberger~~, F F~~]]	+	[[Category: Damberger FF]]
-	[[Category: Daujotyte, D]]	+	[[Category: Daujotyte D]]
-	[[Category: Lukavsky~~, P J~~]]	+	[[Category: Lukavsky PJ]]
-	[[Category: Stuani, C]]	+	[[Category: Stuani C]]
-	[[Category: Tollervey~~, J R~~]]	+	[[Category: Tollervey JR]]
-	[[Category: Ule, J]]	+	[[Category: Ule J]]
-	~~[[Category: Cystic fibrosis]]~~	+
-	~~[[Category: Hammerhead ribozyme]]~~	+
-	~~[[Category: Hnrnp]]~~	+
-	~~[[Category: Isotope-labelled rna]]~~	+
-	~~[[Category: Neurodegeneration]]~~	+
-	~~[[Category: Transcription~~]]	+

OCA at 14:02, 13 March 2019

2019-03-13T14:02:07Z

←Older revision		Revision as of 14:02, 13 March 2019
Line 1:		Line 1:

	==NMR structure of human TDP-43 tandem RRMs in complex with UG-rich RNA==		==NMR structure of human TDP-43 tandem RRMs in complex with UG-rich RNA==
-	<StructureSection load='4bs2' size='340' side='right' caption='[[4bs2]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>	+	<StructureSection load='4bs2' size='340' side='right'caption='[[4bs2]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4bs2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BS2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BS2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4bs2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BS2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BS2 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=4bs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bs2 OCA], [http://pdbe.org/4bs2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bs2 RCSB], [http://www.ebi.ac.uk/pdbsum/4bs2 PDBsum]</span></td></tr>	+	</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=4bs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bs2 OCA], [http://pdbe.org/4bs2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bs2 RCSB], [http://www.ebi.ac.uk/pdbsum/4bs2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bs2 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 4bs2" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4bs2" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tdp-43\|Tdp-43]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Allain, F H.T]]		[[Category: Allain, F H.T]]
	[[Category: Baralle, F E]]		[[Category: Baralle, F E]]

OCA at 17:36, 10 May 2016

2016-05-10T17:36:02Z

←Older revision		Revision as of 17:36, 10 May 2016
Line 1:		Line 1:
		+
	==NMR structure of human TDP-43 tandem RRMs in complex with UG-rich RNA==		==NMR structure of human TDP-43 tandem RRMs in complex with UG-rich RNA==
	<StructureSection load='4bs2' size='340' side='right' caption='[[4bs2]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='4bs2' size='340' side='right' caption='[[4bs2]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4bs2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BS2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BS2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4bs2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BS2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BS2 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=4bs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bs2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bs2 RCSB], [http://www.ebi.ac.uk/pdbsum/4bs2 PDBsum]</span></td></tr>	+	</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=4bs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bs2 OCA], [http://pdbe.org/4bs2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bs2 RCSB], [http://www.ebi.ac.uk/pdbsum/4bs2 PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 17:		Line 18:
	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 4bs2" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 17:38, 21 December 2014

2014-12-21T17:38:52Z

←Older revision		Revision as of 17:38, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4bs2\| PDB=4bs2 \| SCENE= }}~~	+	==NMR structure of human TDP-43 tandem RRMs in complex with UG-rich RNA==
-	===NMR structure of human TDP-43 tandem RRMs in complex with UG-rich RNA===	+	<StructureSection load='4bs2' size='340' side='right' caption='[[4bs2]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
-	~~{{ABSTRACT_PUBMED_24240615}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4bs2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BS2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BS2 FirstGlance]. <br>
-	==Disease==	+	</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=4bs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bs2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bs2 RCSB], [http://www.ebi.ac.uk/pdbsum/4bs2 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 encodes an alternative-splicing regulator with tandem RNA-recognition motifs (RRMs). The protein regulates cystic fibrosis transmembrane regulator (CFTR) exon 9 splicing through binding to long UG-rich RNA sequences and is found in cytoplasmic inclusions of several neurodegenerative diseases. We solved the solution structure of the TDP-43 RRMs in complex with UG-rich RNA. Ten nucleotides are bound by both RRMs, and six are recognized sequence specifically. Among these, a central G interacts with both RRMs and stabilizes a new tandem RRM arrangement. Mutations that eliminate recognition of this key nucleotide or crucial inter-RRM interactions disrupt RNA binding and TDP-43-dependent splicing regulation. In contrast, point mutations that affect base-specific recognition in either RRM have weaker effects. Our findings reveal not only how TDP-43 recognizes UG repeats but also how RNA binding-dependent inter-RRM interactions are crucial for TDP-43 function.

-	~~==About this Structure==~~	+	Molecular basis of UG-rich RNA recognition by the human splicing factor TDP-43.,Lukavsky PJ, Daujotyte D, Tollervey JR, Ule J, Stuani C, Buratti E, Baralle FE, Damberger FF, Allain FH Nat Struct Mol Biol. 2013 Nov 17. doi: 10.1038/nsmb.2698. PMID:24240615<ref>PMID:24240615</ref>
-	~~[[4bs2]] is a 2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Human Human]~~. ~~Full experimental information is available from [http~~:/~~/oca~~.~~weizmann~~.~~ac.il~~/~~oca-bin/ocashort?id=4BS2 OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:024240615</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Allain, F H.T.]]	+	[[Category: Allain, F H.T]]
-	[[Category: Baralle, F E.]]	+	[[Category: Baralle, F E]]
-	[[Category: Buratti, E.]]	+	[[Category: Buratti, E]]
-	[[Category: Damberger, F F.]]	+	[[Category: Damberger, F F]]
-	[[Category: Daujotyte, D.]]	+	[[Category: Daujotyte, D]]
-	[[Category: Lukavsky, P J.]]	+	[[Category: Lukavsky, P J]]
-	[[Category: Stuani, C.]]	+	[[Category: Stuani, C]]
-	[[Category: Tollervey, J R.]]	+	[[Category: Tollervey, J R]]
-	[[Category: Ule, J.]]	+	[[Category: Ule, J]]
	[[Category: Cystic fibrosis]]		[[Category: Cystic fibrosis]]
	[[Category: Hammerhead ribozyme]]		[[Category: Hammerhead ribozyme]]

OCA at 09:03, 27 November 2013

2013-11-27T09:03:14Z

←Older revision		Revision as of 09:03, 27 November 2013
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	{{STRUCTURE_4bs2\| PDB=4bs2 \| SCENE= }}		{{STRUCTURE_4bs2\| PDB=4bs2 \| SCENE= }}
	===NMR structure of human TDP-43 tandem RRMs in complex with UG-rich RNA===		===NMR structure of human TDP-43 tandem RRMs in complex with UG-rich RNA===
		+	{{ABSTRACT_PUBMED_24240615}}

	==Disease==		==Disease==
Line 12:		Line 13:

	==Reference==		==Reference==
-	<references group="xtra"/><references/>	+	<ref group="xtra">PMID:024240615</ref><references group="xtra"/><references/>
	[[Category: Human]]		[[Category: Human]]
	[[Category: Allain, F H.T.]]		[[Category: Allain, F H.T.]]

OCA at 12:26, 20 November 2013

2013-11-20T12:26:17Z

←Older revision		Revision as of 12:26, 20 November 2013
Line 9:		Line 9:

	==About this Structure==		==About this Structure==
-	[[4bs2]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BS2 OCA].	+	[[4bs2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BS2 OCA].

	==Reference==		==Reference==
	<references group="xtra"/><references/>		<references group="xtra"/><references/>
		+	[[Category: Human]]
	[[Category: Allain, F H.T.]]		[[Category: Allain, F H.T.]]
	[[Category: Baralle, F E.]]		[[Category: Baralle, F E.]]

OCA at 08:25, 13 November 2013

2013-11-13T08:25:36Z

←Older revision		Revision as of 08:25, 13 November 2013
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4bs2\| PDB=4bs2 \| SCENE= }}
		+	===NMR structure of human TDP-43 tandem RRMs in complex with UG-rich RNA===

-	~~The~~ entry ~~4bs2~~ 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~~: ~~Lukavsky, P~~.J.~~, Daujotyte, D~~.~~, Tollervey, J~~.R.~~, Ule, J~~., ~~Stuani, C~~.~~, Buratti, E~~.~~, Baralle, F.E., Damberger, F.F., Allain, F.H.T~~.	+	==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: NMR~~ structure ~~of human TDP~~-~~43 tandem RRMs in complex with UG~~-~~rich RNA~~	+	==About this Structure==
		+	[[4bs2]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BS2 OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: Allain, F H.T.]]
		+	[[Category: Baralle, F E.]]
		+	[[Category: Buratti, E.]]
		+	[[Category: Damberger, F F.]]
		+	[[Category: Daujotyte, D.]]
		+	[[Category: Lukavsky, P J.]]
		+	[[Category: Stuani, C.]]
		+	[[Category: Tollervey, J R.]]
		+	[[Category: Ule, J.]]
		+	[[Category: Cystic fibrosis]]
		+	[[Category: Hammerhead ribozyme]]
		+	[[Category: Hnrnp]]
		+	[[Category: Isotope-labelled rna]]
		+	[[Category: Neurodegeneration]]
		+	[[Category: Transcription]]

OCA at 06:20, 28 August 2013

2013-08-28T06:20:23Z

←Older revision		Revision as of 06:20, 28 August 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4bs2 is ON HOLD	+	The entry 4bs2 is ON HOLD until Paper Publication

	Authors: Lukavsky, P.J., Daujotyte, D., Tollervey, J.R., Ule, J., Stuani, C., Buratti, E., Baralle, F.E., Damberger, F.F., Allain, F.H.T.		Authors: Lukavsky, P.J., Daujotyte, D., Tollervey, J.R., Ule, J., Stuani, C., Buratti, E., Baralle, F.E., Damberger, F.F., Allain, F.H.T.

	Description: NMR structure of human TDP-43 tandem RRMs in complex with UG-rich RNA		Description: NMR structure of human TDP-43 tandem RRMs in complex with UG-rich RNA

OCA: Protected "4bs2" [edit=sysop:move=sysop]

2013-06-19T10:56:35Z

Protected "4bs2" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:56, 19 June 2013