View source for 9tki


==TAF15 amyloid filament fold E variant 2==
<StructureSection load='9tki' size='340' side='right'caption='[[9tki]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9tki]] is a 4 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=9TKI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9TKI 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]] 2.39&#8491;</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=9tki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9tki OCA], [https://pdbe.org/9tki PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9tki RCSB], [https://www.ebi.ac.uk/pdbsum/9tki PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9tki ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/RBP56_HUMAN RBP56_HUMAN] Extraskeletal myxoid chondrosarcoma. A chromosomal aberration involving TAF15/TAF2N is found in a form of extraskeletal myxoid chondrosarcomas (EMC). Translocation t(9;17)(q22;q11) with NR4A3.
== Function ==
[https://www.uniprot.org/uniprot/RBP56_HUMAN RBP56_HUMAN] RNA and ssDNA-binding protein that may play specific roles during transcription initiation at distinct promoters. Can enter the preinitiation complex together with the RNA polymerase II (Pol II).<ref>PMID:19124016</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Neurodegenerative diseases are characterised by the assembly of a limited number of disease-specific proteins into amyloid filaments, which form intracellular inclusions or extracellular deposits in the central nervous system (CNS)(1,2). We previously found that amyloid filaments of TATA-binding protein-associated factor 15 (TAF15) characterise a subtype of frontotemporal lobar degeneration with FET protein-immunoreactive inclusions (FTLD-FET)(3), termed atypical FTLD with ubiquitin-positive inclusions (aFTLD-U)(4), which causes early-onset, rapidly progressive behavioural variant frontotemporal dementia (FTD). However, it was not clear if TAF15 proteinopathy was more widespread in neurodegenerative diseases. Two additional FTLD-FET subtypes have been proposed, neuronal intermediate filament inclusion body disease (NIFID) and basophilic inclusion body disease (BIBD)(5,6), which have more heterogenous clinical presentations including FTD, motor neuron diseases (MND) and movement disorders. Here, we used electron cryo-microscopy (cryo-EM) to determine a total of 32 amyloid filament structures from the brains of 17 individuals encompassing all three proposed subtypes of FTLD-FET and their diverse clinical presentations. All cases were characterised by TAF15 filaments, in the absence of filaments of the other FET proteins, fused in sarcoma (FUS) and Ewing's sarcoma (EWS). All three aFTLD-U cases had the previously-reported TAF15 fold(3). Unexpectedly, we found four distinct TAF15 folds among 11 NIFID cases. Eight of these cases shared a common fold, while the remaining three were each distinct. Furthermore, we found distinct TAF15 folds for each of the three BIBD cases. Neuropathological reassessment of the neocortical TAF15 inclusion pathology of these cases distinguished the NIFID cases with the common fold from the others. Thus, TAF15 filament structures form the basis of a new, expanded classification of FTLD-FET subtypes. Moreover, we discovered a TAF15 Y38C variant in the filament fold of one of the individuals with BIBD. The structure is unable to incorporate wild-type TAF15, despite the individual being heterozygous, suggesting that this variant drives TAF15 filament assembly. This study provides structural and genetic evidence that TAF15 amyloid filaments underlie the diverse group of neurodegenerative diseases currently termed FTLD-FET, which we therefore rename FTLD-TAF15.

Distinct TAF15 amyloid filament folds define multiple subtypes of FTLD-TAF15.,Tetter S, Varghese NR, Murzin AG, De Coster W, Van den Broeck M, Roeber S, Joseph JT, Newell K, Castellani R, Das S, Ang LC, Synofzik M, Herms J, Rademakers R, Ghetti B, Lashley T, Mackenzie IRA, Neumann M, Ryskeldi-Falcon B bioRxiv [Preprint]. 2026 Jan 12:2026.01.12.698957. doi: , 10.64898/2026.01.12.698957. PMID:41648099<ref>PMID:41648099</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9tki" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ryskeldi-Falcon B]]
[[Category: Tetter S]]
[[Category: Varghese NR]]