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- EMDB-26281: TMEM106B(120-254) singlet amyloid fibril from dementia with Lewy ... -

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Basic information

Entry
Database: EMDB / ID: EMD-26281
TitleTMEM106B(120-254) singlet amyloid fibril from dementia with Lewy bodies (DLB).
Map dataTMEM106B(120-254) singlet amyloid fibril from DLB.
Sample
  • Complex: TMEM106B(120-254) singlet amyloid fibril from dementia with Lewy bodies (DLB).
Biological speciesHomo sapiens (human)
Methodhelical reconstruction / cryo EM / Resolution: 7.6 Å
AuthorsChang A / Xiang X / Wang J / Lee C / Arakhamia T / Simjanoska M / Wang C / Carlomagno Y / Zhang G / Dhingra S ...Chang A / Xiang X / Wang J / Lee C / Arakhamia T / Simjanoska M / Wang C / Carlomagno Y / Zhang G / Dhingra S / Thierry M / Perneel J / Heeman B / Forgrave LM / DeTure M / DeMarco ML / Cook CN / Rademakers R / Dickson D / Petrucelli L / Stowell MHB / Mackenzie IRA / Fitzpatrick AWP
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)UO1NS110438 United States
CitationJournal: Cell / Year: 2022
Title: Homotypic fibrillization of TMEM106B across diverse neurodegenerative diseases.
Authors: Andrew Chang / Xinyu Xiang / Jing Wang / Carolyn Lee / Tamta Arakhamia / Marija Simjanoska / Chi Wang / Yari Carlomagno / Guoan Zhang / Shikhar Dhingra / Manon Thierry / Jolien Perneel / ...Authors: Andrew Chang / Xinyu Xiang / Jing Wang / Carolyn Lee / Tamta Arakhamia / Marija Simjanoska / Chi Wang / Yari Carlomagno / Guoan Zhang / Shikhar Dhingra / Manon Thierry / Jolien Perneel / Bavo Heeman / Lauren M Forgrave / Michael DeTure / Mari L DeMarco / Casey N Cook / Rosa Rademakers / Dennis W Dickson / Leonard Petrucelli / Michael H B Stowell / Ian R A Mackenzie / Anthony W P Fitzpatrick /
Abstract: Misfolding and aggregation of disease-specific proteins, resulting in the formation of filamentous cellular inclusions, is a hallmark of neurodegenerative disease with characteristic filament ...Misfolding and aggregation of disease-specific proteins, resulting in the formation of filamentous cellular inclusions, is a hallmark of neurodegenerative disease with characteristic filament structures, or conformers, defining each proteinopathy. Here we show that a previously unsolved amyloid fibril composed of a 135 amino acid C-terminal fragment of TMEM106B is a common finding in distinct human neurodegenerative diseases, including cases characterized by abnormal aggregation of TDP-43, tau, or α-synuclein protein. A combination of cryoelectron microscopy and mass spectrometry was used to solve the structures of TMEM106B fibrils at a resolution of 2.7 Å from postmortem human brain tissue afflicted with frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP, n = 8), progressive supranuclear palsy (PSP, n = 2), or dementia with Lewy bodies (DLB, n = 1). The commonality of abundant amyloid fibrils composed of TMEM106B, a lysosomal/endosomal protein, to a broad range of debilitating human disorders indicates a shared fibrillization pathway that may initiate or accelerate neurodegeneration.
History
DepositionFeb 20, 2022-
Header (metadata) releaseApr 20, 2022-
Map releaseApr 20, 2022-
UpdateApr 27, 2022-
Current statusApr 27, 2022Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_26281.map.gz / Format: CCP4 / Size: 75.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationTMEM106B(120-254) singlet amyloid fibril from DLB.
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.07 Å/pix.
x 270 pix.
= 289.98 Å
1.07 Å/pix.
x 270 pix.
= 289.98 Å
1.07 Å/pix.
x 270 pix.
= 289.98 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.074 Å
Density
Contour LevelBy AUTHOR: 0.004
Minimum - Maximum-0.005706155 - 0.015168557
Average (Standard dev.)0.0004726212 (±0.0016461846)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions270270270
Spacing270270270
CellA=B=C: 289.98 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : TMEM106B(120-254) singlet amyloid fibril from dementia with Lewy ...

EntireName: TMEM106B(120-254) singlet amyloid fibril from dementia with Lewy bodies (DLB).
Components
  • Complex: TMEM106B(120-254) singlet amyloid fibril from dementia with Lewy bodies (DLB).

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Supramolecule #1: TMEM106B(120-254) singlet amyloid fibril from dementia with Lewy ...

SupramoleculeName: TMEM106B(120-254) singlet amyloid fibril from dementia with Lewy bodies (DLB).
type: complex / Chimera: Yes / ID: 1 / Parent: 0
Source (natural)Organism: Homo sapiens (human)

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Experimental details

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Structure determination

Methodcryo EM
Processinghelical reconstruction
Aggregation statefilament

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Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 1.4000000000000001 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Final reconstructionApplied symmetry - Helical parameters - Δz: 4.8 Å
Applied symmetry - Helical parameters - Δ&Phi: -0.4 °
Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric)
Resolution.type: BY AUTHOR / Resolution: 7.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 8400
Final angle assignmentType: NOT APPLICABLE

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