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-Structure paper
| タイトル | Assembly of recombinant tau into filaments identical to those of Alzheimer's disease and chronic traumatic encephalopathy. |
|---|---|
| ジャーナル・号・ページ | Elife, Vol. 11, Year 2022 |
| 掲載日 | 2022年3月4日 |
 著者 | Sofia Lövestam / Fujiet Adrian Koh / Bart van Knippenberg / Abhay Kotecha / Alexey G Murzin / Michel Goedert / Sjors H W Scheres /   |
| PubMed 要旨 | Abundant filamentous inclusions of tau are characteristic of more than 20 neurodegenerative diseases that are collectively termed tauopathies. Electron cryo-microscopy (cryo-EM) structures of tau ...Abundant filamentous inclusions of tau are characteristic of more than 20 neurodegenerative diseases that are collectively termed tauopathies. Electron cryo-microscopy (cryo-EM) structures of tau amyloid filaments from human brain revealed that distinct tau folds characterise many different diseases. A lack of laboratory-based model systems to generate these structures has hampered efforts to uncover the molecular mechanisms that underlie tauopathies. Here, we report in vitro assembly conditions with recombinant tau that replicate the structures of filaments from both Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE), as determined by cryo-EM. Our results suggest that post-translational modifications of tau modulate filament assembly, and that previously observed additional densities in AD and CTE filaments may arise from the presence of inorganic salts, like phosphates and sodium chloride. In vitro assembly of tau into disease-relevant filaments will facilitate studies to determine their roles in different diseases, as well as the development of compounds that specifically bind to these structures or prevent their formation. |
 リンク | Elife / PubMed:35244536 / PubMed Central |
| 手法 | EM (らせん対称) |
| 解像度 | 1.86 - 3.4 Å |
| 構造データ | EMDB-14023, PDB-7qjv: EMDB-14024, PDB-7qjw: EMDB-14025, PDB-7qjx: EMDB-14026, PDB-7qjy: EMDB-14027, PDB-7qjz: EMDB-14028, PDB-7qk1: EMDB-14029, PDB-7qk2: EMDB-14030, PDB-7qk3: EMDB-14038, PDB-7qk5: EMDB-14039, PDB-7qk6: EMDB-14040, PDB-7qkf: EMDB-14041, PDB-7qkg: EMDB-14042, PDB-7qkh: EMDB-14043, PDB-7qki: EMDB-14044, PDB-7qkj: EMDB-14045, PDB-7qkk: EMDB-14046, PDB-7qkl: EMDB-14047, PDB-7qkm: EMDB-14053, PDB-7qku: EMDB-14054, PDB-7qkv: EMDB-14055, PDB-7qkw: EMDB-14056, PDB-7qkx: EMDB-14057, PDB-7qky: EMDB-14058, PDB-7qkz: EMDB-14059, PDB-7ql0: EMDB-14060, PDB-7ql1: EMDB-14061, PDB-7ql2: EMDB-14062, PDB-7ql3: EMDB-14063, PDB-7ql4: EMDB-14316, PDB-7r4t: EMDB-14320, PDB-7r5h: |
| 化合物 |  ChemComp-CL:  ChemComp-K: |
| 由来 |
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 キーワード | PROTEIN FIBRIL /  Neurodegeneration (神経変性疾患) / Amyloid (アミロイド) / Tau / Alzheimer's Disease (アルツハイマー病) / Chronic traumatic encephalopathy (慢性外傷性脳症) |
