8BYN

Chronic traumatic encephalopathy tau filaments with PET ligand flortaucipir

Summary for 8BYN

• Entry DOI: 10.2210/pdb8byn/pdb
• EMDB information: 16329
• Descriptor: Microtubule-associated protein tau, 7-(6-fluoranylpyridin-3-yl)-5~{H}-pyrido[4,3-b]indole (2 entities in total)
• Functional Keywords: chronic traumatic encephalopathy, primary age-related tauopathy, tau filaments, pet ligand, flortaucipir, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 6
• Total formula weight: 277098.84

Authors

Shi, Y.,Ghetti, B.,Goedert, M.,Scheres, S.H.W. (deposition date: 2022-12-13, release date: 2023-01-11, Last modification date: 2023-11-01)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.6 Å)