8BYN

Chronic traumatic encephalopathy tau filaments with PET ligand flortaucipir

8BYN の概要

• エントリーDOI: 10.2210/pdb8byn/pdb
• EMDBエントリー: 16329
• 分子名称: Microtubule-associated protein tau, 7-(6-fluoranylpyridin-3-yl)-5~{H}-pyrido[4,3-b]indole (2 entities in total)
• 機能のキーワード: chronic traumatic encephalopathy, primary age-related tauopathy, tau filaments, pet ligand, flortaucipir, protein fibril
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 277098.84

構造登録者

Shi, Y.,Ghetti, B.,Goedert, M.,Scheres, S.H.W. (登録日: 2022-12-13, 公開日: 2023-01-11, 最終更新日: 2023-11-01)

主引用文献

Shi, Y.,Ghetti, B.,Goedert, M.,Scheres, S.H.W.
Cryo-EM Structures of Chronic Traumatic Encephalopathy Tau Filaments with PET Ligand Flortaucipir.
J.Mol.Biol., 435:168025-168025, 2023

PubMed Abstract: Positron emission tomography (PET) imaging allows monitoring the progression of amyloid aggregation in the living brain. [F]-Flortaucipir is the only approved PET tracer compound for the visualisation of tau aggregation. Here, we describe cryo-EM experiments on tau filaments in the presence and absence of flortaucipir. We used tau filaments isolated from the brain of an individual with Alzheimer's disease (AD), and from the brain of an individual with primary age-related tauopathy (PART) with a co-pathology of chronic traumatic encephalopathy (CTE). Unexpectedly, we were unable to visualise additional cryo-EM density for flortaucipir for AD paired helical or straight filaments (PHFs or SFs), but we did observe density for flortaucipir binding to CTE Type I filaments from the case with PART. In the latter, flortaucipir binds in a 1:1 molecular stoichiometry with tau, adjacent to lysine 353 and aspartate 358. By adopting a tilted geometry with respect to the helical axis, the 4.7 Å distance between neighbouring tau monomers is reconciled with the 3.5 Å distance consistent with π-π-stacking between neighbouring molecules of flortaucipir.

PubMed: 37330290
DOI: 10.1016/j.jmb.2023.168025

実験手法

ELECTRON MICROSCOPY (2.6 Å)