6QJM

Cryo-EM structure of heparin-induced 2N4R tau twister filaments

6QJM の概要

• エントリーDOI: 10.2210/pdb6qjm/pdb
• EMDBエントリー: 4564
• 分子名称: Microtubule-associated protein tau (1 entity in total)
• 機能のキーワード: recombinant tau protein, heparin, filament, cross-beta structure, protein fibril
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 15567.24

構造登録者

Zhang, W.,Falcon, B.,Murzin, A.G.,Fan, J.,Crowther, R.A.,Goedert, M.,Scheres, S.H.W. (登録日: 2019-01-24, 公開日: 2019-02-27, 最終更新日: 2024-05-15)

主引用文献

Zhang, W.,Falcon, B.,Murzin, A.G.,Fan, J.,Crowther, R.A.,Goedert, M.,Scheres, S.H.
Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer's and Pick's diseases.
Elife, 8:-, 2019

PubMed Abstract: Assembly of microtubule-associated protein tau into filamentous inclusions underlies a range of neurodegenerative diseases. Tau filaments adopt different conformations in Alzheimer's and Pick's diseases. Here, we used cryo- and immuno- electron microscopy to characterise filaments that were assembled from recombinant full-length human tau with four (2N4R) or three (2N3R) microtubule-binding repeats in the presence of heparin. 2N4R tau assembles into multiple types of filaments, and the structures of three types reveal similar 'kinked hairpin' folds, in which the second and third repeats pack against each other. 2N3R tau filaments are structurally homogeneous, and adopt a dimeric core, where the third repeats of two tau molecules pack in a parallel manner. The heparin-induced tau filaments differ from those of Alzheimer's or Pick's disease, which have larger cores with different repeat compositions. Our results illustrate the structural versatility of amyloid filaments, and raise questions about the relevance of in vitro assembly.

PubMed: 30720432
DOI: 10.7554/eLife.43584

実験手法

ELECTRON MICROSCOPY (3.3 Å)