7SP1

RNA-induced tau amyloid fibril

7SP1 の概要

• エントリーDOI: 10.2210/pdb7sp1/pdb
• EMDBエントリー: 25364
• 分子名称: Isoform Tau-F of Microtubule-associated protein tau, RNA (5'-R(*AP*AP*AP*AP*AP*AP*AP*AP*AP*A)-3') (2 entities in total)
• 機能のキーワード: amyloid fibril, complex, protein fibril-rna complex, protein fibril/rna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 17
• 化学式量合計: 695292.26

構造登録者

Abskharon, R.,Sawaya, M.R.,Boyer, D.R.,Eisenberg, D.S. (登録日: 2021-11-02, 公開日: 2022-03-30, 最終更新日: 2024-06-05)

主引用文献

Abskharon, R.,Sawaya, M.R.,Boyer, D.R.,Cao, Q.,Nguyen, B.A.,Cascio, D.,Eisenberg, D.S.
Cryo-EM structure of RNA-induced tau fibrils reveals a small C-terminal core that may nucleate fibril formation.
Proc.Natl.Acad.Sci.USA, 119:e2119952119-e2119952119, 2022

PubMed Abstract: In neurodegenerative diseases including Alzheimer’s and amyotrophic lateral sclerosis, proteins that bind RNA are found in aggregated forms in autopsied brains. Evidence suggests that RNA aids nucleation of these pathological aggregates; however, the mechanism has not been investigated at the level of atomic structure. Here, we present the 3.4-Å resolution structure of fibrils of full-length recombinant tau protein in the presence of RNA, determined by electron cryomicroscopy (cryo-EM). The structure reveals the familiar in-register cross-β amyloid scaffold but with a small fibril core spanning residues Glu391 to Ala426, a region disordered in the fuzzy coat in all previously studied tau polymorphs. RNA is bound on the fibril surface to the positively charged residues Arg406 and His407 and runs parallel to the fibril axis. The fibrils dissolve when RNase is added, showing that RNA is necessary for fibril integrity. While this structure cannot exist simultaneously with the tau fibril structures extracted from patients’ brains, it could conceivably account for the nucleating effects of RNA cofactors followed by remodeling as fibrils mature.

PubMed: 35377792
DOI: 10.1073/pnas.2119952119

実験手法

ELECTRON MICROSCOPY (3.4 Å)