7NRS

Conformation 1 of straight filament from primary age-related tauopathy brain

7NRS の概要

• エントリーDOI: 10.2210/pdb7nrs/pdb
• EMDBエントリー: 12550
• 分子名称: Microtubule-associated protein tau (1 entity in total)
• 機能のキーワード: tau filament, protein fibril
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 459198.71

構造登録者

Shi, Y.,Murzin, A.G.,Falcon, B.,Epstein, A.,Machin, J.,Tempest, P.,Newell, K.L.,Vidal, R.,Garringer, H.J.,Sahara, N.,Higuchi, M.,Ghetti, B.,Jang, M.,Scheres, S.H.W.,Goedert, M. (登録日: 2021-03-04, 公開日: 2021-03-24, 最終更新日: 2024-07-10)

主引用文献

Shi, Y.,Murzin, A.G.,Falcon, B.,Epstein, A.,Machin, J.,Tempest, P.,Newell, K.L.,Vidal, R.,Garringer, H.J.,Sahara, N.,Higuchi, M.,Ghetti, B.,Jang, M.K.,Scheres, S.H.W.,Goedert, M.
Cryo-EM structures of tau filaments from Alzheimer's disease with PET ligand APN-1607.
Acta Neuropathol, 141:697-708, 2021

PubMed Abstract: Tau and Aβ assemblies of Alzheimer's disease (AD) can be visualized in living subjects using positron emission tomography (PET). Tau assemblies comprise paired helical and straight filaments (PHFs and SFs). APN-1607 (PM-PBB3) is a recently described PET ligand for AD and other tau proteinopathies. Since it is not known where in the tau folds PET ligands bind, we used electron cryo-microscopy (cryo-EM) to determine the binding sites of APN-1607 in the Alzheimer fold. We identified two major sites in the β-helix of PHFs and SFs and a third major site in the C-shaped cavity of SFs. In addition, we report that tau filaments from posterior cortical atrophy (PCA) and primary age-related tauopathy (PART) are identical to those from AD. In support, fluorescence labelling showed binding of APN-1607 to intraneuronal inclusions in AD, PART and PCA. Knowledge of the binding modes of APN-1607 to tau filaments may lead to the development of new ligands with increased specificity and binding activity. We show that cryo-EM can be used to identify the binding sites of small molecules in amyloid filaments.

PubMed: 33723967
DOI: 10.1007/s00401-021-02294-3

実験手法

ELECTRON MICROSCOPY (2.68 Å)