[English] 日本語
Yorodumi- PDB-7qwg: TMEM106B filaments with Fold IIa from Multiple system atrophy (ca... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7qwg | ||||||
---|---|---|---|---|---|---|---|
Title | TMEM106B filaments with Fold IIa from Multiple system atrophy (case 19) | ||||||
Components | Transmembrane protein 106B | ||||||
Keywords | PROTEIN FIBRIL / Amyloid / neurodegeneration / filament / TMEM106B | ||||||
Function / homology | Function and homology information lysosomal protein catabolic process / regulation of lysosome organization / lysosomal lumen acidification / lysosome localization / lysosomal transport / positive regulation of dendrite development / dendrite morphogenesis / lysosome organization / neuron cellular homeostasis / late endosome membrane ...lysosomal protein catabolic process / regulation of lysosome organization / lysosomal lumen acidification / lysosome localization / lysosomal transport / positive regulation of dendrite development / dendrite morphogenesis / lysosome organization / neuron cellular homeostasis / late endosome membrane / ATPase binding / lysosome / endosome / lysosomal membrane / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.38 Å | ||||||
Authors | Lovestam, S. / Schweighauser, M. / Scheres, S.H.W. | ||||||
Funding support | United Kingdom, 1items
| ||||||
Citation | Journal: Nature / Year: 2022 Title: Age-dependent formation of TMEM106B amyloid filaments in human brains. Authors: Manuel Schweighauser / Diana Arseni / Mehtap Bacioglu / Melissa Huang / Sofia Lövestam / Yang Shi / Yang Yang / Wenjuan Zhang / Abhay Kotecha / Holly J Garringer / Ruben Vidal / Grace I ...Authors: Manuel Schweighauser / Diana Arseni / Mehtap Bacioglu / Melissa Huang / Sofia Lövestam / Yang Shi / Yang Yang / Wenjuan Zhang / Abhay Kotecha / Holly J Garringer / Ruben Vidal / Grace I Hallinan / Kathy L Newell / Airi Tarutani / Shigeo Murayama / Masayuki Miyazaki / Yuko Saito / Mari Yoshida / Kazuko Hasegawa / Tammaryn Lashley / Tamas Revesz / Gabor G Kovacs / John van Swieten / Masaki Takao / Masato Hasegawa / Bernardino Ghetti / Maria Grazia Spillantini / Benjamin Ryskeldi-Falcon / Alexey G Murzin / Michel Goedert / Sjors H W Scheres / 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- ...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. | ||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7qwg.cif.gz | 82.5 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7qwg.ent.gz | 64.2 KB | Display | PDB format |
PDBx/mmJSON format | 7qwg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7qwg_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7qwg_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 7qwg_validation.xml.gz | 28.8 KB | Display | |
Data in CIF | 7qwg_validation.cif.gz | 40.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qw/7qwg ftp://data.pdbj.org/pub/pdb/validation_reports/qw/7qwg | HTTPS FTP |
-Related structure data
Related structure data | 14187MC 7qvcC 7qvfC 7qwlC 7qwmC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 31156.318 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9NUM4 |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
-Sample preparation
Component | Name: TMEM106B / Type: TISSUE / Entity ID: all / Source: NATURAL |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
EM software |
| |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||
Helical symmerty | Angular rotation/subunit: -0.63 ° / Axial rise/subunit: 4.78 Å / Axial symmetry: C1 | |||||||||||||||
3D reconstruction | Resolution: 3.38 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 7347 / Symmetry type: HELICAL |