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==Paired helical filament extracted from GSS Patient brain tissue== | ==Paired helical filament extracted from GSS Patient brain tissue== | ||
<StructureSection load='7mkh' size='340' side='right'caption='[[7mkh]]' scene=''> | <StructureSection load='7mkh' size='340' side='right'caption='[[7mkh]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MKH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MKH FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MKH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MKH FirstGlance]. <br> | ||
</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=7mkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mkh OCA], [https://pdbe.org/7mkh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mkh RCSB], [https://www.ebi.ac.uk/pdbsum/7mkh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mkh ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3Å</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=7mkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mkh OCA], [https://pdbe.org/7mkh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mkh RCSB], [https://www.ebi.ac.uk/pdbsum/7mkh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mkh ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In human neurodegenerative diseases associated with the intracellular aggregation of Tau protein, the ordered cores of Tau filaments adopt distinct folds. Here, we analyze Tau filaments isolated from the brain of individuals affected by Prion-Protein cerebral amyloid angiopathy (PrP-CAA) with a nonsense mutation in the PRNP gene that leads to early termination of translation of PrP (Q160Ter or Q160X), and Gerstmann-Straussler-Scheinker (GSS) disease, with a missense mutation in the PRNP gene that leads to an amino acid substitution at residue 198 (F198S) of PrP. The clinical and neuropathologic phenotypes associated with these two mutations in PRNP are different; however, the neuropathologic analyses of these two genetic variants have consistently shown the presence of numerous neurofibrillary tangles (NFTs) made of filamentous Tau aggregates in neurons. We report that Tau filaments in PrP-CAA (Q160X) and GSS (F198S) are composed of 3-repeat and 4-repeat Tau isoforms, having a striking similarity to NFTs in Alzheimer disease (AD). In PrP-CAA (Q160X), Tau filaments are made of both paired helical filaments (PHFs) and straight filaments (SFs), while in GSS (F198S), only PHFs were found. Mass spectrometry analyses of Tau filaments extracted from PrP-CAA (Q160X) and GSS (F198S) brains show the presence of post-translational modifications that are comparable to those seen in Tau aggregates from AD. Cryo-EM analysis reveals that the atomic models of the Tau filaments obtained from PrP-CAA (Q160X) and GSS (F198S) are identical to those of the Tau filaments from AD, and are therefore distinct from those of Pick disease, chronic traumatic encephalopathy, and corticobasal degeneration. Our data support the hypothesis that in the presence of extracellular amyloid deposits and regardless of the primary amino acid sequence of the amyloid protein, similar molecular mechanisms are at play in the formation of identical Tau filaments. | |||
Structure of Tau filaments in Prion protein amyloidoses.,Hallinan GI, Hoq MR, Ghosh M, Vago FS, Fernandez A, Garringer HJ, Vidal R, Jiang W, Ghetti B Acta Neuropathol. 2021 Aug;142(2):227-241. doi: 10.1007/s00401-021-02336-w. Epub , 2021 Jun 14. PMID:34128081<ref>PMID:34128081</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7mkh" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Microtubule-associated protein 3D structures|Microtubule-associated protein 3D structures]] | |||
*[[Tau protein 3D structures|Tau protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Hoq MR]] | [[Category: Hoq MR]] | ||