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- EMDB-24953: Cryo-EM structure of TMEM106B fibrils extracted from a FTLD-TDP p... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-24953 | |||||||||
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Title | Cryo-EM structure of TMEM106B fibrils extracted from a FTLD-TDP patient, polymorph 1 | |||||||||
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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 / ATPase binding ...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 / ATPase binding / late endosome membrane / endosome / lysosome / lysosomal membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
![]() | Cao Q / Jiang Y / Sawaya MR / Eisenberg DS | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Amyloid fibrils in FTLD-TDP are composed of TMEM106B and not TDP-43. Authors: Yi Xiao Jiang / Qin Cao / Michael R Sawaya / Romany Abskharon / Peng Ge / Michael DeTure / Dennis W Dickson / Janine Y Fu / Rachel R Ogorzalek Loo / Joseph A Loo / David S Eisenberg / ![]() ![]() Abstract: Frontotemporal lobar degeneration (FTLD) is the third most common neurodegenerative condition after Alzheimer's and Parkinson's diseases. FTLD typically presents in 45 to 64 year olds with ...Frontotemporal lobar degeneration (FTLD) is the third most common neurodegenerative condition after Alzheimer's and Parkinson's diseases. FTLD typically presents in 45 to 64 year olds with behavioural changes or progressive decline of language skills. The subtype FTLD-TDP is characterized by certain clinical symptoms and pathological neuronal inclusions with TAR DNA-binding protein (TDP-43) immunoreactivity. Here we extracted amyloid fibrils from brains of four patients representing four of the five FTLD-TDP subclasses, and determined their structures by cryo-electron microscopy. Unexpectedly, all amyloid fibrils examined were composed of a 135-residue carboxy-terminal fragment of transmembrane protein 106B (TMEM106B), a lysosomal membrane protein previously implicated as a genetic risk factor for FTLD-TDP. In addition to TMEM106B fibrils, we detected abundant non-fibrillar aggregated TDP-43 by immunogold labelling. Our observations confirm that FTLD-TDP is associated with amyloid fibrils, and that the fibrils are formed by TMEM106B rather than TDP-43. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 7.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 11.5 KB 11.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.3 KB | Display | ![]() |
Images | ![]() | 66.9 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7saqMC ![]() 7sarC ![]() 7sasC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data size: 3.4 TB Data #1: Unaligned multi-frame micrographs of TMEM106B amyloid fibrils extracted from FTLD-TDP donor 1 [micrographs - multiframe] Data #2: Unaligned multi-frame micrographs of TMEM106B amyloid fibrils extracted from FTLD-TDP donor 2 [micrographs - multiframe] Data #3: Unaligned multi-frame micrographs of TMEM106B amyloid fibrils extracted from FTLD-TDP donor 3 [micrographs - multiframe] Data #4: Unaligned multi-frame micrographs of TMEM106B amyloid fibrils extracted from FTLD-TDP donor 4 [micrographs - multiframe]) |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : TMEM106B fibrils, polymorph 1
Entire | Name: TMEM106B fibrils, polymorph 1 |
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Components |
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-Supramolecule #1: TMEM106B fibrils, polymorph 1
Supramolecule | Name: TMEM106B fibrils, polymorph 1 / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1 Details: Amyloid fibrils extracted from autopsied brain tissues of a donor with FTLD-TDP |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Transmembrane protein 106B
Macromolecule | Name: Transmembrane protein 106B / type: protein_or_peptide / ID: 1 Details: Glycosylation of Asn145, Asn151, Asn164, and Asn183 Number of copies: 5 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 31.156318 KDa |
Sequence | String: MGKSLSHLPL HSSKEDAYDG VTSENMRNGL VNSEVHNEDG RNGDVSQFPY VEFTGRDSVT CPTCQGTGRI PRGQENQLVA LIPYSDQRL RPRRTKLYVM ASVFVCLLLS GLAVFFLFPR SIDVKYIGVK SAYVSYDVQK RTIYLNITNT LNITNNNYYS V EVENITAQ ...String: MGKSLSHLPL HSSKEDAYDG VTSENMRNGL VNSEVHNEDG RNGDVSQFPY VEFTGRDSVT CPTCQGTGRI PRGQENQLVA LIPYSDQRL RPRRTKLYVM ASVFVCLLLS GLAVFFLFPR SIDVKYIGVK SAYVSYDVQK RTIYLNITNT LNITNNNYYS V EVENITAQ VQFSKTVIGK ARLNNITIIG PLDMKQIDYT VPTVIAEEMS YMYDFCTLIS IKVHNIVLMM QVTVTTTYFG HS EQISQER YQYVDCGRNT TYQLGQSEYL NVLQPQQ |
-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: 20 / 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: 7.5 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Detector mode: SUPER-RESOLUTION / Number grids imaged: 1 / Average electron dose: 39.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL / Overall B value: 124 |
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Output model | ![]() PDB-7saq: |