7QVF

TMEM106B filaments with Fold I-d from Multiple system atrophy (case 18)

7QVF の概要

• エントリーDOI: 10.2210/pdb7qvf/pdb
• EMDBエントリー: 14176
• 分子名称: Transmembrane protein 106B (1 entity in total)
• 機能のキーワード: amyloid, neurodegeneration, filament, tmem106b, 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: 186937.91

構造登録者

Lovestam, S.,Schweighauser, M.,Scheres, S.H.W. (登録日: 2022-01-21, 公開日: 2022-03-09, 最終更新日: 2024-11-13)

主引用文献

Schweighauser, M.,Arseni, D.,Bacioglu, M.,Huang, M.,Lovestam, S.,Shi, Y.,Yang, Y.,Zhang, W.,Kotecha, A.,Garringer, H.J.,Vidal, R.,Hallinan, G.I.,Newell, K.L.,Tarutani, A.,Murayama, S.,Miyazaki, M.,Saito, Y.,Yoshida, M.,Hasegawa, K.,Lashley, T.,Revesz, T.,Kovacs, G.G.,van Swieten, J.,Takao, M.,Hasegawa, M.,Ghetti, B.,Spillantini, M.G.,Ryskeldi-Falcon, B.,Murzin, A.G.,Goedert, M.,Scheres, S.H.W.
Age-dependent formation of TMEM106B amyloid filaments in human brains.
Nature, 605:310-314, 2022

PubMed Abstract: Many age-dependent neurodegenerative diseases, such as Alzheimer's and Parkinson's, are characterized by abundant inclusions of amyloid filaments. Filamentous inclusions of the proteins tau, amyloid-β, α-synuclein and transactive response DNA-binding protein (TARDBP; also known as TDP-43) are the most common. Here we used structure determination by cryogenic electron microscopy to show that residues 120-254 of the lysosomal type II transmembrane protein 106B (TMEM106B) also form amyloid filaments in human brains. We determined the structures of TMEM106B filaments from a number of brain regions of 22 individuals with abundant amyloid deposits, including those resulting from sporadic and inherited tauopathies, amyloid-β amyloidoses, synucleinopathies and TDP-43 proteinopathies, as well as from the frontal cortex of 3 individuals with normal neurology and no or only a few amyloid deposits. We observed three TMEM106B folds, with no clear relationships between folds and diseases. TMEM106B filaments correlated with the presence of a 29-kDa sarkosyl-insoluble fragment and globular cytoplasmic inclusions, as detected by an antibody specific to the carboxy-terminal region of TMEM106B. The identification of TMEM106B filaments in the brains of older, but not younger, individuals with normal neurology indicates that they form in an age-dependent manner.

PubMed: 35344985
DOI: 10.1038/s41586-022-04650-z

実験手法

ELECTRON MICROSCOPY (3.64 Å)