EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	How short peptides can disassemble ultra-stable tau fibrils extracted from Alzheimer's disease brain by a strain-relief mechanism.
ジャーナル・号・ページ	bioRxiv, Year 2024
掲載日	2024年3月29日
著者	Ke Hou / Peng Ge / Michael R Sawaya / Joshua L Dolinsky / Yuan Yang / Yi Xiao Jiang / Liisa Lutter / David R Boyer / Xinyi Cheng / Justin Pi / Jeffrey Zhang / Jiahui Lu / Shixin Yang / Zhiheng Yu / Juli Feigon / David S Eisenberg
PubMed 要旨	Reducing fibrous aggregates of protein tau is a possible strategy for halting progression of Alzheimer's disease (AD). Previously we found that the D-peptide D-TLKIVWC disassembles tau fibrils from ...Reducing fibrous aggregates of protein tau is a possible strategy for halting progression of Alzheimer's disease (AD). Previously we found that 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.
リンク	bioRxiv / PubMed:38585812 / PubMed Central
手法	EM (らせん対称)
解像度	3.1 - 3.7 Å
構造データ	44181 9b4i EMDB-44181, PDB-9b4i: Filament of D-TLKIVWI, a D-peptide that disaggregates Alzheimer's Paired Helical Filaments, determined by Cryo-EM 手法: EM (らせん対称) / 解像度: 3.6 Å 44182 9b4j EMDB-44182, PDB-9b4j: Filament of D-TLKIVWS, a D-peptide that disaggregates Alzheimer's Paired Helical Filaments, determined by Cryo-EM 手法: EM (らせん対称) / 解像度: 3.5 Å 44183 9b4k EMDB-44183, PDB-9b4k: Filament of D-TLKIVWR, a D-peptide that disaggregates Alzheimer's Paired Helical Filaments, determined by Cryo-EM 手法: EM (らせん対称) / 解像度: 3.7 Å 44184 9b4l EMDB-44184, PDB-9b4l: Filament of Tau in complex with D-TLKIVWI, a D-peptide that disaggregates Alzheimer's Paired Helical Filaments, determined by Cryo-EM 手法: EM (らせん対称) / 解像度: 3.1 Å 44185 9b4m EMDB-44185, PDB-9b4m: Filament of Tau in complex with D-TLKIVWS, a D-peptide that disaggregates Alzheimer's Paired Helical Filaments, determined by Cryo-EM 手法: EM (らせん対称) / 解像度: 3.1 Å 44186 9b4n EMDB-44186, PDB-9b4n: Filament of Tau in complex with D-TLKIVWR, a D-peptide that disaggregates Alzheimer's Paired Helical Filaments, determined by Cryo-EM 手法: EM (らせん対称) / 解像度: 3.5 Å 44187 9b4o EMDB-44187, PDB-9b4o: Alzheimer's Tau Paired Helical Filaments, determined by CryoEM, before addition of D-peptide disaggregants 手法: EM (らせん対称) / 解像度: 3.5 Å
化合物	ChemComp-EDT: {[-(BIS-CARBOXYMETHYL-AMINO)-ETHYL]-CARBOXYMETHYL-AMINO}-ACETIC ACID / EDTA
由来	synthetic construct (人工物) homo sapiens (ヒト)
キーワード	UNKNOWN FUNCTION / Alzheimer's disease / Tau / fibril / cryo-EM / helix / PROTEIN FIBRIL