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- PDB-7u11: TMEM106B(120-254) protofilament from frontotemporal lobar degener... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7u11 | ||||||
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Title | TMEM106B(120-254) protofilament from frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) type A (case 1) | ||||||
![]() | Transmembrane protein 106B | ||||||
![]() | PROTEIN FIBRIL / TMEM106B / Amyloid fibril | ||||||
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 | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
![]() | Fitzpatrick, A.W.P. / Stowell, M.H.B. / Chang, A. / Xiang, X. / Wang, J. / Lee, C. / Arakhamia, T. / Simjanoska, M. / Wang, C. / Carlomagno, Y. ...Fitzpatrick, A.W.P. / Stowell, M.H.B. / 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, L.M. / DeTure, M. / DeMarco, M.L. / Cook, C.N. / Rademakers, R. / Dickson, D. / Petrucelli, L. / Mackenzie, I.R.A. | ||||||
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
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 82.1 KB | Display | ![]() |
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PDB format | ![]() | 66.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 26274MC ![]() 7u0zC ![]() 7u10C ![]() 7u12C ![]() 7u13C ![]() 7u14C ![]() 7u15C ![]() 7u16C ![]() 7u17C ![]() 7u18C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Symmetry | Helical symmetry: (Circular symmetry: 1 / Dyad axis: no / N subunits divisor: 1 / Num. of operations: 3 / Rise per n subunits: 4.8 Å / Rotation per n subunits: -0.4 °) |
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Components
#1: Protein | Mass: 15502.680 Da / Num. of mol.: 3 / Fragment: UNP residues 120-254 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Sugar | ChemComp-NAG / Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
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Sample preparation
Component | Name: TMEM106B(120-254) singlet amyloid fibril from dementia with Lewy bodies (DLB) Type: COMPLEX / Entity ID: #1 / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2800 nm / Nominal defocus min: 1400 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: -0.4 ° / Axial rise/subunit: 4.8 Å / Axial symmetry: C1 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 58000 / Symmetry type: HELICAL | ||||||||||||||||||||||||
Refine LS restraints |
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