8FNZ

Acetylated tau repeat 1 and 2 fragment (AcR1R2)

8FNZ の概要

• エントリーDOI: 10.2210/pdb8fnz/pdb
• EMDBエントリー: 28721
• 分子名称: Microtubule-associated protein tau, acetylated repeat 1 and 2 fragment (1 entity in total)
• 機能のキーワード: amyloid motif acetylation tau repeat domain post-translational modification, protein fibril
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 48
• 化学式量合計: 99520.90

構造登録者

Li, L.,Nguyen, A.B.,Mullapudi, V.,Joachimiak, L. (登録日: 2022-12-29, 公開日: 2023-06-28, 最終更新日: 2024-10-23)

主引用文献

Li, L.,Nguyen, B.A.,Mullapudi, V.,Li, Y.,Saelices, L.,Joachimiak, L.A.
Disease-associated patterns of acetylation stabilize tau fibril formation.
Structure, 31:1025-1037.e4, 2023

PubMed Abstract: Assembly of tau into beta-sheet-rich amyloids dictates the pathology of a diversity of diseases. Lysine acetylation has been proposed to drive tau amyloid assembly, but no direct mechanism has emerged. Using tau fragments, we identify patterns of acetylation that flank amyloidogenic motifs on the tau fragments that promote rapid fibril assembly. We determined a 3.9 Å cryo-EM amyloid fibril structure assembled from an acetylated tau fragment uncovering how lysine acetylation can mediate gain-of-function interactions. Comparison of the structure to an ex vivo tauopathy fibril reveals regions of structural similarity. Finally, we show that fibrils encoding disease-associated patterns of acetylation are active in cell-based tau aggregation assays. Our data uncover the dual role of lysine residues in limiting tau aggregation while their acetylation leads to stabilizing pro-aggregation interactions. Design of tau sequence with specific acetylation patterns may lead to controllable tau aggregation to direct folding of tau into distinct amyloid folds.

PubMed: 37348495
DOI: 10.1016/j.str.2023.05.020

実験手法

ELECTRON MICROSCOPY (3.88 Å)