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- EMDB-26278: TMEM106B(120-254) singlet amyloid fibril from frontotemporal loba... -
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Open data
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Basic information
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Title | TMEM106B(120-254) singlet amyloid fibril from frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) type B case 2 (case 7). | |||||||||
![]() | TMEM106B(120-254) singlet amyloid fibril from frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) type B case 2 (case 7). | |||||||||
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Function / homology | ![]() lysosomal protein catabolic process / regulation of lysosome organization / lysosomal lumen acidification / lysosome localization / positive regulation of dendrite development / dendrite morphogenesis / lysosomal transport / lysosome organization / neuron cellular homeostasis / late endosome membrane ...lysosomal protein catabolic process / regulation of lysosome organization / lysosomal lumen acidification / lysosome localization / positive regulation of dendrite development / dendrite morphogenesis / lysosomal transport / lysosome organization / neuron cellular homeostasis / late endosome membrane / ATPase binding / lysosome / endosome / lysosomal membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
![]() | Fitzpatrick AWP / Stowell MHB / Chang A / Xiang X / Wang J / Lee C / Arakhamia T / Simjanoska M / Wang C / Carlomagno Y ...Fitzpatrick AWP / Stowell MHB / 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 / Mackenzie IRA | |||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 12.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 11.6 KB 11.6 KB | Display Display | ![]() |
Images | ![]() | 156.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7u15MC ![]() 7u17MC ![]() 7u0zC ![]() 7u10C ![]() 7u11C ![]() 7u12C ![]() 7u13C ![]() 7u14C ![]() 7u16C ![]() 7u18C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Map
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Annotation | TMEM106B(120-254) singlet amyloid fibril from frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) type B case 2 (case 7). | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.047 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : TMEM106B(120-254) singlet amyloid fibril from dementia with Lewy ...
Entire | Name: TMEM106B(120-254) singlet amyloid fibril from dementia with Lewy bodies (DLB). |
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Components |
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-Supramolecule #1: TMEM106B(120-254) singlet amyloid fibril from dementia with Lewy ...
Supramolecule | Name: TMEM106B(120-254) singlet amyloid fibril from dementia with Lewy bodies (DLB). type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Transmembrane protein 106B
Macromolecule | Name: Transmembrane protein 106B / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 15.50268 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: SIDVKYIGVK SAYVSYDVQK RTIYLNITNT LNITNNNYYS VEVENITAQV QFSKTVIGKA RLNNITIIGP LDMKQIDYTV PTVIAEEMS YMYDFCTLIS IKVHNIVLMM QVTVTTTYFG HSEQISQERY QYVDCG |
-Macromolecule #2: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 12 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | helical reconstruction |
Aggregation state | filament |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination 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 reconstruction | Applied symmetry - Helical parameters - Δz: 4.8 Å Applied symmetry - Helical parameters - Δ&Phi: -0.67 ° Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric) Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 31000 |
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Final angle assignment | Type: NOT APPLICABLE |