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1wf0, 20 NMR models ()
Gene: HEP00195 (Homo sapiens)
Resources: FirstGlance, OCA, RCSB, PDBsum, TOPSAN
Coordinates: save as pdb, mmCIF, xml


Solution structure of RRM domain in TAR DNA-binding protein-43


[TADBP_HUMAN] Defects in TARDBP are the cause of amyotrophic lateral sclerosis type 10 (ALS10) [MIM: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.[1][2][3][4][5][6][7][8][9][10][11][12][13]


[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.[14][15]

About this Structure

1wf0 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA.


  1. Elden AC, Kim HJ, Hart MP, Chen-Plotkin AS, Johnson BS, Fang X, Armakola M, Geser F, Greene R, Lu MM, Padmanabhan A, Clay-Falcone D, McCluskey L, Elman L, Juhr D, Gruber PJ, Rub U, Auburger G, Trojanowski JQ, Lee VM, Van Deerlin VM, Bonini NM, Gitler AD. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature. 2010 Aug 26;466(7310):1069-75. doi: 10.1038/nature09320. PMID:20740007 doi:10.1038/nature09320
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  6. Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, Ackerley S, Durnall JC, Williams KL, Buratti E, Baralle F, de Belleroche J, Mitchell JD, Leigh PN, Al-Chalabi A, Miller CC, Nicholson G, Shaw CE. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science. 2008 Mar 21;319(5870):1668-72. doi: 10.1126/science.1154584. Epub 2008, Feb 28. PMID:18309045 doi:10.1126/science.1154584
  7. Benajiba L, Le Ber I, Camuzat A, Lacoste M, Thomas-Anterion C, Couratier P, Legallic S, Salachas F, Hannequin D, Decousus M, Lacomblez L, Guedj E, Golfier V, Camu W, Dubois B, Campion D, Meininger V, Brice A. TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration. Ann Neurol. 2009 Apr;65(4):470-3. doi: 10.1002/ana.21612. PMID:19350673 doi:10.1002/ana.21612
  8. Corrado L, Ratti A, Gellera C, Buratti E, Castellotti B, Carlomagno Y, Ticozzi N, Mazzini L, Testa L, Taroni F, Baralle FE, Silani V, D'Alfonso S. High frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis. Hum Mutat. 2009 Apr;30(4):688-94. doi: 10.1002/humu.20950. PMID:19224587 doi:10.1002/humu.20950
  9. Borroni B, Bonvicini C, Alberici A, Buratti E, Agosti C, Archetti S, Papetti A, Stuani C, Di Luca M, Gennarelli M, Padovani A. Mutation within TARDBP leads to frontotemporal dementia without motor neuron disease. Hum Mutat. 2009 Nov;30(11):E974-83. doi: 10.1002/humu.21100. PMID:19655382 doi:10.1002/humu.21100
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  11. Chio A, Borghero G, Pugliatti M, Ticca A, Calvo A, Moglia C, Mutani R, Brunetti M, Ossola I, Marrosu MG, Murru MR, Floris G, Cannas A, Parish LD, Cossu P, Abramzon Y, Johnson JO, Nalls MA, Arepalli S, Chong S, Hernandez DG, Traynor BJ, Restagno G. Large proportion of amyotrophic lateral sclerosis cases in Sardinia due to a single founder mutation of the TARDBP gene. Arch Neurol. 2011 May;68(5):594-8. doi: 10.1001/archneurol.2010.352. Epub 2011, Jan 10. PMID:21220647 doi:10.1001/archneurol.2010.352
  12. Orru S, Manolakos E, Orru N, Kokotas H, Mascia V, Carcassi C, Petersen MB. High frequency of the TARDBP p.Ala382Thr mutation in Sardinian patients with amyotrophic lateral sclerosis. Clin Genet. 2012 Feb;81(2):172-8. doi: 10.1111/j.1399-0004.2011.01668.x. Epub, 2011 Apr 18. PMID:21418058 doi:10.1111/j.1399-0004.2011.01668.x
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  14. Strong MJ, Volkening K, Hammond R, Yang W, Strong W, Leystra-Lantz C, Shoesmith C. TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein. Mol Cell Neurosci. 2007 Jun;35(2):320-7. Epub 2007 Mar 20. PMID:17481916 doi:10.1016/j.mcn.2007.03.007
  15. Buratti E, Dork T, Zuccato E, Pagani F, Romano M, Baralle FE. Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping. EMBO J. 2001 Apr 2;20(7):1774-84. PMID:11285240 doi:10.1093/emboj/20.7.1774

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