8qxa
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==TDP-43 amyloid fibrils: Morphology-1b== | |
| + | <StructureSection load='8qxa' size='340' side='right'caption='[[8qxa]], [[Resolution|resolution]] 4.05Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8qxa]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8QXA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QXA FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.05Å</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=8qxa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qxa OCA], [https://pdbe.org/8qxa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qxa RCSB], [https://www.ebi.ac.uk/pdbsum/8qxa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qxa ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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> | ||
| + | == 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The transactive response DNA-binding protein-43 (TDP-43) is a multi-facet protein involved in phase separation, RNA-binding, and alternative splicing. In the context of neurodegenerative diseases, abnormal aggregation of TDP-43 has been linked to amyotrophic lateral sclerosis and frontotemporal lobar degeneration through the aggregation of its C-terminal domain. Here, we report a cryo-electron microscopy (cryo-EM)-based structural characterization of TDP-43 fibrils obtained from the full-length protein. We find that the fibrils are polymorphic and contain three different amyloid structures. The structures differ in the number and relative orientation of the protofilaments, although they share a similar fold containing an amyloid key motif. The observed fibril structures differ from previously described conformations of TDP-43 fibrils and help to better understand the structural landscape of the amyloid fibril structures derived from this protein. | ||
| - | + | Cryo-EM observation of the amyloid key structure of polymorphic TDP-43 amyloid fibrils.,Sharma K, Stockert F, Shenoy J, Berbon M, Abdul-Shukkoor MB, Habenstein B, Loquet A, Schmidt M, Fandrich M Nat Commun. 2024 Jan 12;15(1):486. doi: 10.1038/s41467-023-44489-0. PMID:38212334<ref>PMID:38212334</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8qxa" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Faendrich M]] | ||
| + | [[Category: Loquet A]] | ||
| + | [[Category: Schmidt M]] | ||
| + | [[Category: Sharma K]] | ||
| + | [[Category: Shenoy J]] | ||
Current revision
TDP-43 amyloid fibrils: Morphology-1b
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