8Q2K

Tau - AD-MIA3

8Q2K の概要

• エントリーDOI: 10.2210/pdb8q2k/pdb
• EMDBエントリー: 18111
• 分子名称: Isoform Tau-D of Microtubule-associated protein tau (1 entity in total)
• 機能のキーワード: amyloid, tau, protein fibril
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 240016.64

構造登録者

Lovestam, S.,Li, D.,Scheres, S.H.W.,Goedert, M. (登録日: 2023-08-02, 公開日: 2023-08-30, 最終更新日: 2024-01-24)

主引用文献

Lovestam, S.,Li, D.,Wagstaff, J.L.,Kotecha, A.,Kimanius, D.,McLaughlin, S.H.,Murzin, A.G.,Freund, S.M.V.,Goedert, M.,Scheres, S.H.W.
Disease-specific tau filaments assemble via polymorphic intermediates.
Nature, 625:119-125, 2024

PubMed Abstract: Intermediate species in the assembly of amyloid filaments are believed to play a central role in neurodegenerative diseases and may constitute important targets for therapeutic intervention. However, structural information about intermediate species has been scarce and the molecular mechanisms by which amyloids assemble remain largely unknown. Here we use time-resolved cryogenic electron microscopy to study the in vitro assembly of recombinant truncated tau (amino acid residues 297-391) into paired helical filaments of Alzheimer's disease or into filaments of chronic traumatic encephalopathy. We report the formation of a shared first intermediate amyloid filament, with an ordered core comprising residues 302-316. Nuclear magnetic resonance indicates that the same residues adopt rigid, β-strand-like conformations in monomeric tau. At later time points, the first intermediate amyloid disappears and we observe many different intermediate amyloid filaments, with structures that depend on the reaction conditions. At the end of both assembly reactions, most intermediate amyloids disappear and filaments with the same ordered cores as those from human brains remain. Our results provide structural insights into the processes of primary and secondary nucleation of amyloid assembly, with implications for the design of new therapies.

PubMed: 38030728
DOI: 10.1038/s41586-023-06788-w

実験手法

ELECTRON MICROSCOPY (2.88 Å)