- EMDB-35409: Chronic traumatic encephalopathy type I tau filaments from primar... -
+
データを開く
IDまたはキーワード:
読み込み中...
-
基本情報
登録情報
データベース: EMDB / ID: EMD-35409
タイトル
Chronic traumatic encephalopathy type I tau filaments from primary age-related tauopathy brain incubated with DMSO without PET ligand flortaucipir (-flortaucipir)
マップデータ
試料
組織: Sarkosyl-insoluble fraction from the hippocampus of an individual with primary age-related tauopathy
タンパク質・ペプチド: Microtubule-associated protein tau
キーワード
Primary age-related tauopathy / Chronic traumatic encephalopathy type I tau filaments / PET ligand / Flortaucipir / PROTEIN FIBRIL
National Institutes of Health/National Institute on Aging (NIH/NIA)
P30-AG010133
米国
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
UO1-NS110437
米国
National Institutes of Health/National Institute on Aging (NIH/NIA)
RF1-AG071177
米国
引用
ジャーナル: J Mol Biol / 年: 2023 タイトル: Cryo-EM Structures of Chronic Traumatic Encephalopathy Tau Filaments with PET Ligand Flortaucipir. 著者: Yang Shi / Bernardino Ghetti / Michel Goedert / Sjors H W Scheres / 要旨: 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 ...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.