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 disassemble tau fibrils in Alzheimer's disease.
ジャーナル・号・ページ	Nature, Vol. 644, Issue 8078, Page 1020-1027, Year 2025
掲載日	2025年7月9日
著者	Ke Hou / Peng Ge / Michael R Sawaya / Liisa Lutter / Joshua L Dolinsky / Yuan Yang / Yi Xiao Jiang / David R Boyer / Xinyi Cheng / Justin Pi / Jeffrey Zhang / Jiahui Lu / Romany Abskharon / Shixin Yang / Zhiheng Yu / Juli Feigon / David S Eisenberg /
PubMed 要旨	Reducing fibrous aggregates of the protein tau is a possible strategy for halting the progression of Alzheimer's disease (AD). Previously, we found that in vitro, the D-enantiomeric peptide (D- ...Reducing fibrous aggregates of the protein tau is a possible strategy for halting the progression of Alzheimer's disease (AD). Previously, we found that in vitro, the D-enantiomeric peptide (D-peptide) D-TLKIVWC disassembles ultra-stable tau fibrils extracted from the autopsied brains of individuals with AD (hereafter, these tau fibrils are referred to as AD-tau) into benign segments, with no energy source other than ambient thermal agitation. To consider D-peptide-mediated disassembly as a potential route to therapeutics for AD, it is essential to understand the mechanism and energy source of the disassembly action. Here, we show that the assembly of D-peptides into amyloid-like ('mock-amyloid') fibrils is essential for AD-tau disassembly. These mock-amyloid fibrils have a right-handed twist but are constrained to adopt a left-handed twist when templated in complex with AD-tau. The release of strain that accompanies the conversion of left-twisted to right-twisted, relaxed mock-amyloid produces a torque that is sufficient to break the local hydrogen bonding between tau molecules, and leads to the fragmentation of AD-tau. This strain-relief mechanism seems to operate in other examples of amyloid fibril disassembly, and could inform the development of first-in-class therapeutics for amyloid diseases.
リンク	Nature / PubMed:40634605 / 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