5mrg - Revision history

OCA at 17:47, 8 November 2023

OCA — Wed, 08 Nov 2023 17:47:10 GMT

←Older revision		Revision as of 17:47, 8 November 2023
Line 1:		Line 1:

	==Solution structure of TDP-43 (residues 1-102)==		==Solution structure of TDP-43 (residues 1-102)==
-	<StructureSection load='5mrg' size='340' side='right'caption='[[5mrg~~]], [[NMR_Ensembles_of_Models \| 20 NMR models~~]]' scene=''>	+	<StructureSection load='5mrg' size='340' side='right'caption='[[5mrg]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mrg]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MRG OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5MRG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mrg]] is a 1 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=5MRG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MRG FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5mrg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mrg OCA], [~~http~~://pdbe.org/5mrg PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5mrg RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5mrg PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5mrg ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=5mrg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mrg OCA], [https://pdbe.org/5mrg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mrg RCSB], [https://www.ebi.ac.uk/pdbsum/5mrg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mrg 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 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5mrg" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5mrg" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Tdp-43\|Tdp-43]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Baralle~~, F E~~]]	+	[[Category: Baralle FE]]
-	[[Category: Laurents~~, D V~~]]	+	[[Category: Laurents DV]]
-	[[Category: Mompean, M]]	+	[[Category: Mompean M]]
-	[[Category: Pantoja-Uceda, D]]	+	[[Category: Pantoja-Uceda D]]
-	[[Category: Romano, V]]	+	[[Category: Romano V]]
-	[[Category: Stuani, C]]	+	[[Category: Stuani C]]
-	~~[[Category: Dna binding protein]]~~	+
-	~~[[Category: Structure from cyana 3 97~~]]	+

OCA at 07:26, 19 August 2020

OCA — Wed, 19 Aug 2020 07:26:47 GMT

←Older revision		Revision as of 07:26, 19 August 2020
Line 1:		Line 1:

	==Solution structure of TDP-43 (residues 1-102)==		==Solution structure of TDP-43 (residues 1-102)==
-	<StructureSection load='5mrg' size='340' side='right' caption='[[5mrg]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>	+	<StructureSection load='5mrg' size='340' side='right'caption='[[5mrg]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mrg]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MRG OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5MRG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mrg]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MRG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MRG 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=5mrg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mrg OCA], [http://pdbe.org/5mrg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mrg RCSB], [http://www.ebi.ac.uk/pdbsum/5mrg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mrg ProSAT]</span></td></tr>	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mrg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mrg OCA], [http://pdbe.org/5mrg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mrg RCSB], [http://www.ebi.ac.uk/pdbsum/5mrg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mrg ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5mrg" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5mrg" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tdp-43\|Tdp-43]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Baralle, F E]]		[[Category: Baralle, F E]]
	[[Category: Laurents, D V]]		[[Category: Laurents, D V]]

OCA at 10:51, 3 August 2017

OCA — Thu, 03 Aug 2017 10:51:18 GMT

←Older revision		Revision as of 10:51, 3 August 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5mrg is ~~ON HOLD~~ ~~until sometime~~ in the ~~future~~	+	==Solution structure of TDP-43 (residues 1-102)==
		+	<StructureSection load='5mrg' size='340' side='right' caption='[[5mrg]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5mrg]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MRG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MRG 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=5mrg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mrg OCA], [http://pdbe.org/5mrg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mrg RCSB], [http://www.ebi.ac.uk/pdbsum/5mrg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mrg ProSAT]</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>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Transactive response DNA-binding protein 43 (TDP-43) performs multiple tasks in mRNA processing, transport, and translational regulation, but it also forms aggregates implicated in amyotrophic lateral sclerosis. TDP-43's N-terminal domain (NTD) is important for these activities and dysfunctions; however, there is an open debate about whether or not it adopts a specifically folded, stable structure. Here, we studied NTD mutations designed to destabilize its structure utilizing NMR and fluorescence spectroscopies, analytical ultracentrifugation, splicing assays, and cell microscopy. The substitutions V31R and T32R abolished TDP-43 activity in splicing and aggregation processes, and even the rather mild L28A mutation severely destabilized the NTD, drastically reducing TDP-43's in vitro splicing activity and inducing aberrant localization and aggregation in cells. These findings strongly support the idea that a stably folded NTD is essential for correct TDP-43 function. The stably folded NTD also promotes dimerization, which is pertinent to the protein's activities and pathological aggregation, and we present an atomic-level structural model for the TDP-43 dimer based on NMR data. Leu-27 is evolutionarily well conserved even though it is exposed in the monomeric NTD. We found here that Leu-27 is buried in the dimer and that the L27A mutation promotes monomerization. In conclusion, our study sheds light on the structural and biological properties of the TDP-43 NTD, indicating that the NTD must be stably folded for TDP-43's physiological functions, and has implications for understanding the mechanisms promoting the pathological aggregation of this protein.

-	~~Authors: Mompean~~, M., ~~Romano~~, V., Pantoja-Uceda, D., Stuani, C., Baralle, F.E., Laurents~~, D~~.V.	+	Point mutations in the N-terminal domain of transactive response DNA-binding protein 43 kDa (TDP-43) compromise its stability, dimerization, and functions.,Mompean M, Romano V, Pantoja-Uceda D, Stuani C, Baralle FE, Buratti E, Laurents DV J Biol Chem. 2017 Jul 14;292(28):11992-12006. doi: 10.1074/jbc.M117.775965. Epub , 2017 May 31. PMID:28566288<ref>PMID:28566288</ref>

-	~~Description: Solution structure~~ of ~~TDP~~-~~43 (residues 1~~-~~102)~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Pantoja-Uceda~~, D]]	+	<div class="pdbe-citations 5mrg" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Baralle, F E]]
		+	[[Category: Laurents, D V]]
	[[Category: Mompean, M]]		[[Category: Mompean, M]]
		+	[[Category: Pantoja-Uceda, D]]
	[[Category: Romano, V]]		[[Category: Romano, V]]
	[[Category: Stuani, C]]		[[Category: Stuani, C]]
-	[[Category: ~~Baralle, F.E~~]]	+	[[Category: Dna binding protein]]
-	[[Category: ~~Laurents, D.V~~]]	+	[[Category: Structure from cyana 3 97]]

OCA at 11:34, 9 March 2017

OCA — Thu, 09 Mar 2017 11:34:47 GMT

←Older revision		Revision as of 11:34, 9 March 2017
Line 7:		Line 7:
	Description: Solution structure of TDP-43 (residues 1-102)		Description: Solution structure of TDP-43 (residues 1-102)
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Stuani, C]]
-	[[Category: Laurents, D.V]]
	[[Category: Pantoja-Uceda, D]]		[[Category: Pantoja-Uceda, D]]
	[[Category: Mompean, M]]		[[Category: Mompean, M]]
	[[Category: Romano, V]]		[[Category: Romano, V]]
		+	[[Category: Stuani, C]]
	[[Category: Baralle, F.E]]		[[Category: Baralle, F.E]]
		+	[[Category: Laurents, D.V]]

OCA at 13:07, 18 January 2017

OCA — Wed, 18 Jan 2017 13:07:12 GMT

←Older revision		Revision as of 13:07, 18 January 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5mrg is ON HOLD	+	The entry 5mrg is ON HOLD until sometime in the future

	Authors: Mompean, M., Romano, V., Pantoja-Uceda, D., Stuani, C., Baralle, F.E., Laurents, D.V.		Authors: Mompean, M., Romano, V., Pantoja-Uceda, D., Stuani, C., Baralle, F.E., Laurents, D.V.

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

OCA — Wed, 04 Jan 2017 14:18:45 GMT

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

←Older revision

Revision as of 14:18, 4 January 2017

OCA: New page: '''Unreleased structure''' The entry 5mrg is ON HOLD Authors: Mompean, M., Romano, V., Pantoja-Uceda, D., Stuani, C., Baralle, F.E., Laurents, D.V. Description: Solution structure of T...

OCA — Wed, 04 Jan 2017 14:18:44 GMT

New page: '''Unreleased structure''' The entry 5mrg is ON HOLD Authors: Mompean, M., Romano, V., Pantoja-Uceda, D., Stuani, C., Baralle, F.E., Laurents, D.V. Description: Solution structure of T...

New page

'''Unreleased structure'''

The entry 5mrg is ON HOLD

Authors: Mompean, M., Romano, V., Pantoja-Uceda, D., Stuani, C., Baralle, F.E., Laurents, D.V.

Description: Solution structure of TDP-43 (residues 1-102)
[[Category: Unreleased Structures]]
[[Category: Stuani, C]]
[[Category: Laurents, D.V]]
[[Category: Pantoja-Uceda, D]]
[[Category: Mompean, M]]
[[Category: Romano, V]]
[[Category: Baralle, F.E]]