7QWG
TMEM106B filaments with Fold IIa from Multiple system atrophy (case 19)
Summary for 7QWG
| Entry DOI | 10.2210/pdb7qwg/pdb |
| EMDB information | 14187 |
| Descriptor | Transmembrane protein 106B (1 entity in total) |
| Functional Keywords | amyloid, neurodegeneration, filament, tmem106b, protein fibril |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 3 |
| Total formula weight | 93468.95 |
| Authors | Lovestam, S.,Schweighauser, M.,Scheres, S.H.W. (deposition date: 2022-01-25, release date: 2022-03-09, Last modification date: 2024-11-13) |
| Primary citation | 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 Cited by 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: 35344985DOI: 10.1038/s41586-022-04650-z PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.38 Å) |
Structure validation
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