Tdp-43

From Proteopedia

TDP-43 helical stabilizers

spinqualitylabelsall models Compound A is the best current binder to the healthy helical tdp-43 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037571/) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image This is the healthy helical coil (residues 307-349) of TDP-43. A key biomolecular cause of ALS appears to be a helix-sheet transition in this area, leading to the formation of protein fibrils. Function Tdp-43 or TAR DNA-binding protein 43 is a heterogeneous nuclear ribonucleoprotein which has crucial roles in gene expression and alternative splicing, stress response, neuronal functions such as neurite outgrowth and many other cellular processes[1]. Disease Tdp-43 mutations were found ion familial and sporadic ALS patients[2]. Phosphorylated Tdp-43 is deposited as cytoplasmic and intranuclear inclusions in brains of patients with frontotemporal lobar degeneration and ALS[3]. Structural highlights This is a sample scene created with SAT to by Group, and another to make of the protein.

3D Structures of Tdp-43

Updated on 17-March-2018

2cqg – hTDP-43 RRM1 domain – human - NMR
1wf0 – hTDP-43 RRM2 domain - NMR
5mrg, 2n4p, 5x4f – hTDP-43 N-terminal domain - NMR
5mdi – hTDP-43 N-terminal domain
2n2c, 2n3x – hTDP-43 prion-like helix - NMR
2n4g, 2n4h – hTDP-43 prion-like helix (mutant) - NMR
4y0f, 4iuf – hTDP-43 RRM1 domain + DNA
4y00 – hTDP-43 RRM1 domain (mutant) + DNA
4bs2 – hTDP-43 RRM1+RRM2 domains + RNA - NMR
3d2w – TDP-43 RRM2 domain + DNA - mouse

References

1. ↑ Buratti E, Baralle FE. Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease. Front Biosci. 2008 Jan 1;13:867-78. PMID:17981595
2. ↑ 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
3. ↑ Hasegawa M, Arai T, Nonaka T, Kametani F, Yoshida M, Hashizume Y, Beach TG, Buratti E, Baralle F, Morita M, Nakano I, Oda T, Tsuchiya K, Akiyama H. Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Ann Neurol. 2008 Jul;64(1):60-70. doi: 10.1002/ana.21425. PMID:18546284 doi:http://dx.doi.org/10.1002/ana.21425