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Cryo-EM structures of tau filaments from Alzheimer’s disease with PET ligand APN-1607
https://repo.qst.go.jp/records/82299
https://repo.qst.go.jp/records/822997bd367cb-4ac5-49e2-90a7-481057a68716
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-03-19 | |||||
| タイトル | ||||||
| タイトル | Cryo-EM structures of tau filaments from Alzheimer’s disease with PET ligand APN-1607 | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Shi, Yang
× Shi, Yang× G Murzin, Alexey× Falcon, Benjamin× Epstein, Alexander× Machin, Jonathan× Tempest, Paul× L Newell, Kathy× Vidal, Ruben× J Garringer, Holly× Sahara, Naruhiko× Higuchi, Makoto× Ghetti, Bernardino× Ming-Kuei, Jang× H W Scheres, Sjors× Goedert, Michel× Naruhiko, Sahara× Makoto, Higuchi |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. | |||||
| 書誌情報 |
Acta neuropathologica 巻 141, p. 697-708, 発行日 2021-03 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0001-6322 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 33723967 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1007/s00401-021-02294-3 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://link.springer.com/article/10.1007/s00401-021-02294-3 | |||||
