9b4j
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Filament of D-TLKIVWS, a D-peptide that disaggregates Alzheimer's Paired Helical Filaments, determined by Cryo-EM== | |
| + | <StructureSection load='9b4j' size='340' side='right'caption='[[9b4j]], [[Resolution|resolution]] 3.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9b4j]] is a 60 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9B4J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9B4J 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]] 3.5Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DIL:D-ISOLEUCINE'>DIL</scene>, <scene name='pdbligand=DLE:D-LEUCINE'>DLE</scene>, <scene name='pdbligand=DLY:D-LYSINE'>DLY</scene>, <scene name='pdbligand=DSN:D-SERINE'>DSN</scene>, <scene name='pdbligand=DTH:D-THREONINE'>DTH</scene>, <scene name='pdbligand=DTR:D-TRYPTOPHAN'>DTR</scene>, <scene name='pdbligand=DVA:D-VALINE'>DVA</scene></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=9b4j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9b4j OCA], [https://pdbe.org/9b4j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9b4j RCSB], [https://www.ebi.ac.uk/pdbsum/9b4j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9b4j ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Reducing fibrous aggregates of protein tau is a possible strategy for halting progression of Alzheimer's disease (AD). Previously we found that in vitro the D-peptide D-TLKIVWC disassembles tau fibrils from AD brains (AD-tau) into benign segments with no energy source present beyond ambient thermal agitation. This disassembly by a short peptide was unexpected, given that AD-tau is sufficiently stable to withstand disassembly in boiling SDS detergent. To consider D peptide-mediated disassembly as a potential therapeutic for AD, it is essential to understand the mechanism and energy source of the disassembly action. We find assembly of D-peptides into amyloid-like fibrils is essential for tau fibril disassembly. Cryo-EM and atomic force microscopy reveal that these D-peptide fibrils have a right-handed twist and embrace tau fibrils which have a left-handed twist. In binding to the AD-tau fibril, the oppositely twisted D-peptide fibril produces a strain, which is relieved by disassembly of both fibrils. This strain-relief mechanism appears to operate in other examples of amyloid fibril disassembly and provides a new direction for the development of first-in-class therapeutics for amyloid diseases. | ||
| - | + | How short peptides can disassemble ultra-stable tau fibrils extracted from Alzheimer's disease brain by a strain-relief mechanism.,Hou K, Ge P, Sawaya MR, Dolinsky JL, Yang Y, Jiang YX, Lutter L, Boyer DR, Cheng X, Pi J, Zhang J, Lu J, Yang S, Yu Z, Feigon J, Eisenberg DS bioRxiv [Preprint]. 2024 Mar 29:2024.03.25.586668. doi: , 10.1101/2024.03.25.586668. PMID:38585812<ref>PMID:38585812</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9b4j" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Synthetic construct]] | ||
| + | [[Category: Eisenberg DS]] | ||
| + | [[Category: Ge P]] | ||
| + | [[Category: Hou K]] | ||
| + | [[Category: Sawaya MR]] | ||
Current revision
Filament of D-TLKIVWS, a D-peptide that disaggregates Alzheimer's Paired Helical Filaments, determined by Cryo-EM
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