+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-16999 | |||||||||||||||
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Title | TAF15 amyloid fold in atypical FTLD - Individual 1 | |||||||||||||||
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Sample |
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Keywords | amyloid / amyloid-forming protein / neurodegeneration / RNA BINDING PROTEIN | |||||||||||||||
Function / homology | Function and homology information mRNA stabilization / HIV Transcription Initiation / RNA Polymerase II HIV Promoter Escape / Transcription of the HIV genome / RNA Polymerase II Promoter Escape / RNA Polymerase II Transcription Pre-Initiation And Promoter Opening / RNA Polymerase II Transcription Initiation / RNA Polymerase II Transcription Initiation And Promoter Clearance / transcription coregulator activity / RNA Polymerase II Pre-transcription Events ...mRNA stabilization / HIV Transcription Initiation / RNA Polymerase II HIV Promoter Escape / Transcription of the HIV genome / RNA Polymerase II Promoter Escape / RNA Polymerase II Transcription Pre-Initiation And Promoter Opening / RNA Polymerase II Transcription Initiation / RNA Polymerase II Transcription Initiation And Promoter Clearance / transcription coregulator activity / RNA Polymerase II Pre-transcription Events / RNA splicing / mRNA 3'-UTR binding / Regulation of TP53 Activity through Phosphorylation / positive regulation of DNA-templated transcription / DNA binding / RNA binding / nucleoplasm / nucleus / metal ion binding / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | helical reconstruction / cryo EM / Resolution: 1.97 Å | |||||||||||||||
Authors | Tetter S / Ryskeldi-Falcon B | |||||||||||||||
Funding support | United Kingdom, Switzerland, 4 items
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Citation | Journal: Nature / Year: 2024 Title: TAF15 amyloid filaments in frontotemporal lobar degeneration. Authors: Stephan Tetter / Diana Arseni / Alexey G Murzin / Yazead Buhidma / Sew Y Peak-Chew / Holly J Garringer / Kathy L Newell / Ruben Vidal / Liana G Apostolova / Tammaryn Lashley / Bernardino ...Authors: Stephan Tetter / Diana Arseni / Alexey G Murzin / Yazead Buhidma / Sew Y Peak-Chew / Holly J Garringer / Kathy L Newell / Ruben Vidal / Liana G Apostolova / Tammaryn Lashley / Bernardino Ghetti / Benjamin Ryskeldi-Falcon / Abstract: Frontotemporal lobar degeneration (FTLD) causes frontotemporal dementia (FTD), the most common form of dementia after Alzheimer's disease, and is often also associated with motor disorders. The ...Frontotemporal lobar degeneration (FTLD) causes frontotemporal dementia (FTD), the most common form of dementia after Alzheimer's disease, and is often also associated with motor disorders. The pathological hallmarks of FTLD are neuronal inclusions of specific, abnormally assembled proteins. In the majority of cases the inclusions contain amyloid filament assemblies of TAR DNA-binding protein 43 (TDP-43) or tau, with distinct filament structures characterizing different FTLD subtypes. The presence of amyloid filaments and their identities and structures in the remaining approximately 10% of FTLD cases are unknown but are widely believed to be composed of the protein fused in sarcoma (FUS, also known as translocated in liposarcoma). As such, these cases are commonly referred to as FTLD-FUS. Here we used cryogenic electron microscopy (cryo-EM) to determine the structures of amyloid filaments extracted from the prefrontal and temporal cortices of four individuals with FTLD-FUS. Surprisingly, we found abundant amyloid filaments of the FUS homologue TATA-binding protein-associated factor 15 (TAF15, also known as TATA-binding protein-associated factor 2N) rather than of FUS itself. The filament fold is formed from residues 7-99 in the low-complexity domain (LCD) of TAF15 and was identical between individuals. Furthermore, we found TAF15 filaments with the same fold in the motor cortex and brainstem of two of the individuals, both showing upper and lower motor neuron pathology. The formation of TAF15 amyloid filaments with a characteristic fold in FTLD establishes TAF15 proteinopathy in neurodegenerative disease. The structure of TAF15 amyloid filaments provides a basis for the development of model systems of neurodegenerative disease, as well as for the design of diagnostic and therapeutic tools targeting TAF15 proteinopathy. | |||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_16999.map.gz | 25.4 MB | EMDB map data format | |
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Header (meta data) | emd-16999-v30.xml emd-16999.xml | 16.2 KB 16.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_16999_fsc.xml | 9.1 KB | Display | FSC data file |
Images | emd_16999.png | 57.7 KB | ||
Masks | emd_16999_msk_1.map | 64 MB | Mask map | |
Filedesc metadata | emd-16999.cif.gz | 5.9 KB | ||
Others | emd_16999_half_map_1.map.gz emd_16999_half_map_2.map.gz | 49.6 MB 49.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-16999 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16999 | HTTPS FTP |
-Validation report
Summary document | emd_16999_validation.pdf.gz | 974.4 KB | Display | EMDB validaton report |
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Full document | emd_16999_full_validation.pdf.gz | 974 KB | Display | |
Data in XML | emd_16999_validation.xml.gz | 16.3 KB | Display | |
Data in CIF | emd_16999_validation.cif.gz | 21.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16999 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16999 | HTTPS FTP |
-Related structure data
Related structure data | 8onsMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_16999.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.824 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_16999_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_16999_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_16999_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : TAF15 atypical FTLD amyloid fold
Entire | Name: TAF15 atypical FTLD amyloid fold |
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Components |
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-Supramolecule #1: TAF15 atypical FTLD amyloid fold
Supramolecule | Name: TAF15 atypical FTLD amyloid fold / type: tissue / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) / Organ: brain / Tissue: frontal and temporal lobe |
-Macromolecule #1: TATA-binding protein-associated factor 2N
Macromolecule | Name: TATA-binding protein-associated factor 2N / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 61.909 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MSDSGSYGQS GGEQQSYSTY GNPGSQGYGQ ASQSYSGYGQ TTDSSYGQNY SGYSSYGQSQ SGYSQSYGGY ENQKQSSYSQ QPYNNQGQQ QNMESSGSQG GRAPSYDQPD YGQQDSYDQQ SGYDQHQGSY DEQSNYDQQH DSYSQNQQSY HSQRENYSHH T QDDRRDVS ...String: MSDSGSYGQS GGEQQSYSTY GNPGSQGYGQ ASQSYSGYGQ TTDSSYGQNY SGYSSYGQSQ SGYSQSYGGY ENQKQSSYSQ QPYNNQGQQ QNMESSGSQG GRAPSYDQPD YGQQDSYDQQ SGYDQHQGSY DEQSNYDQQH DSYSQNQQSY HSQRENYSHH T QDDRRDVS RYGEDNRGYG GSQGGGRGRG GYDKDGRGPM TGSSGGDRGG FKNFGGHRDY GPRTDADSES DNSDNNTIFV QG LGEGVST DQVGEFFKQI GIIKTNKKTG KPMINLYTDK DTGKPKGEAT VSFDDPPSAK AAIDWFDGKE FHGNIIKVSF ATR RPEFMR GGGSGGGRRG RGGYRGRGGF QGRGGDPKSG DWVCPNPSCG NMNFARRNSC NQCNEPRPED SRPSGGDFRG RGYG GERGY RGRGGRGGDR GGYGGDRSGG GYGGDRSSGG GYSGDRSGGG YGGDRSGGGY GGDRGGGYGG DRGGGYGGDR GGGYG GDRG GYGGDRGGGY GGDRGGYGGD RGGYGGDRGG YGGDRGGYGG DRSRGGYGGD RGGGSGYGGD RSGGYGGDRS GGGYGG DRG GGYGGDRGGY GGKMGGRNDY RNDQRNRPY UniProtKB: TATA-binding protein-associated factor 2N |
-Macromolecule #2: water
Macromolecule | Name: water / type: ligand / ID: 2 / Number of copies: 115 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.4 / Details: 100 mM NaCl, 10 mM Tris-HCl, pH 7.4 |
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 200 / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |