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Tdp-43

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TDP-43 helical stabilizers
TDP-43 helical stabilizers
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<StructureSection load='2n2cligalza0.pdb.gz' size='600' side='right' caption='Compound A is the best current binder to the healthy helical tdp-43' scene=''>
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<StructureSection load='2n2cligalza0.pdb.gz' size='350' side='right' caption='Compound A is the best current binder to the healthy helical tdp-43 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037571/)' scene=''>
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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. '''Tdp-43'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.
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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.
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You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
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== Function ==
== Function ==
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'''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<ref>PMID:17981595</ref>.
== Disease ==
== Disease ==
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== Relevance ==
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Tdp-43 mutations were found ion familial and sporadic ALS patients<ref>PMID:18309045</ref>. Phosphorylated Tdp-43 is deposited as cytoplasmic and intranuclear inclusions in brains of patients with frontotemporal lobar degeneration and ALS<ref>PMID:18546284</ref>.
== Structural highlights ==
== Structural highlights ==
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This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
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This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein.
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</StructureSection>
</StructureSection>
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== 3D Structures of Tdp-43 ==
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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[[2cqg]] – hTDP-43 RRM1 domain – human - NMR <br />
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[[1wf0]] – hTDP-43 RRM2 domain - NMR <br />
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[[5mrg]], [[2n4p]], [[5x4f]] – hTDP-43 N-terminal domain - NMR <br />
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[[5mdi]] – hTDP-43 N-terminal domain <br />
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[[2n2c]], [[2n3x]] – hTDP-43 prion-like helix - NMR <br />
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[[2n4g]], [[2n4h]] – hTDP-43 prion-like helix (mutant) - NMR <br />
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[[4y0f]], [[4iuf]] – hTDP-43 RRM1 domain + DNA <br />
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[[4y00]] – hTDP-43 RRM1 domain (mutant) + DNA <br />
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[[4bs2]] – hTDP-43 RRM1+RRM2 domains + RNA - NMR<br />
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[[3d2w]] – TDP-43 RRM2 domain + DNA - mouse<br />
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== References ==
== References ==
<references/>
<references/>

Current revision

TDP-43 helical stabilizers

Compound A is the best current binder to the healthy helical tdp-43 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037571/)

Drag the structure with the mouse to rotate

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

Proteopedia Page Contributors and Editors (what is this?)

Gerry Lushington, Michal Harel

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