6VHL

Paired Helical Filament from Alzheimer's Disease Human Brain Tissue

6VHL の概要

• エントリーDOI: 10.2210/pdb6vhl/pdb
• EMDBエントリー: 21207
• 分子名称: Microtubule-associated protein tau, GLYCINE (2 entities in total)
• 機能のキーワード: pathological amyloid fibril cross-beta fold parallel beta-sheets, protein fibril
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 17041.42

構造登録者

Arakhamia, T.,Lee, C.E.,Carlomagno, Y.,Duong, D.M.,Kundinger, S.R.,Wang, K.,Williams, D.,DeTure, M.,Dickson, D.W.,Cook, C.N.,Seyfried, N.T.,Petrucelli, L.,Fitzpatrick, A.W.P. (登録日: 2020-01-10, 公開日: 2020-03-04, 最終更新日: 2024-03-06)

主引用文献

Arakhamia, T.,Lee, C.E.,Carlomagno, Y.,Duong, D.M.,Kundinger, S.R.,Wang, K.,Williams, D.,DeTure, M.,Dickson, D.W.,Cook, C.N.,Seyfried, N.T.,Petrucelli, L.,Fitzpatrick, A.W.P.
Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains.
Cell, 180:633-644.e12, 2020

PubMed Abstract: Tau aggregation into insoluble filaments is the defining pathological hallmark of tauopathies. However, it is not known what controls the formation and templated seeding of strain-specific structures associated with individual tauopathies. Here, we use cryo-electron microscopy (cryo-EM) to determine the structures of tau filaments from corticobasal degeneration (CBD) human brain tissue. Cryo-EM and mass spectrometry of tau filaments from CBD reveal that this conformer is heavily decorated with posttranslational modifications (PTMs), enabling us to map PTMs directly onto the structures. By comparing the structures and PTMs of tau filaments from CBD and Alzheimer's disease, it is found that ubiquitination of tau can mediate inter-protofilament interfaces. We propose a structure-based model in which cross-talk between PTMs influences tau filament structure, contributing to the structural diversity of tauopathy strains. Our approach establishes a framework for further elucidating the relationship between the structures of polymorphic fibrils, including their PTMs, and neurodegenerative disease.

PubMed: 32032505
DOI: 10.1016/j.cell.2020.01.027

実験手法

ELECTRON MICROSCOPY (3.3 Å)