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- EMDB-4565: Cryo-EM reconstruction of heparin-induced 2N4R tau jagged filaments -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-4565 | |||||||||
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Title | Cryo-EM reconstruction of heparin-induced 2N4R tau jagged filaments | |||||||||
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Function / homology | ![]() plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / axonal transport / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex ...plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / axonal transport / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex / phosphatidylinositol bisphosphate binding / main axon / regulation of long-term synaptic depression / negative regulation of kinase activity / negative regulation of tubulin deacetylation / generation of neurons / positive regulation of protein localization / rRNA metabolic process / internal protein amino acid acetylation / regulation of chromosome organization / regulation of mitochondrial fission / axonal transport of mitochondrion / intracellular distribution of mitochondria / axon development / central nervous system neuron development / regulation of microtubule polymerization / microtubule polymerization / minor groove of adenine-thymine-rich DNA binding / lipoprotein particle binding / dynactin binding / glial cell projection / apolipoprotein binding / negative regulation of mitochondrial membrane potential / protein polymerization / axolemma / negative regulation of mitochondrial fission / Caspase-mediated cleavage of cytoskeletal proteins / regulation of microtubule polymerization or depolymerization / positive regulation of axon extension / regulation of microtubule cytoskeleton organization / Activation of AMPK downstream of NMDARs / supramolecular fiber organization / cytoplasmic microtubule organization / regulation of cellular response to heat / stress granule assembly / regulation of calcium-mediated signaling / axon cytoplasm / positive regulation of microtubule polymerization / somatodendritic compartment / synapse assembly / cellular response to brain-derived neurotrophic factor stimulus / phosphatidylinositol binding / nuclear periphery / cellular response to nerve growth factor stimulus / positive regulation of superoxide anion generation / protein phosphatase 2A binding / regulation of autophagy / astrocyte activation / response to lead ion / synapse organization / microglial cell activation / Hsp90 protein binding / regulation of synaptic plasticity / PKR-mediated signaling / protein homooligomerization / memory / microtubule cytoskeleton organization / SH3 domain binding / cellular response to reactive oxygen species / cytoplasmic ribonucleoprotein granule / activation of cysteine-type endopeptidase activity involved in apoptotic process / microtubule cytoskeleton / neuron projection development / cell-cell signaling / protein-macromolecule adaptor activity / actin binding / single-stranded DNA binding / protein-folding chaperone binding / cellular response to heat / cell body / growth cone / microtubule binding / double-stranded DNA binding / microtubule / amyloid fibril formation / sequence-specific DNA binding / dendritic spine / learning or memory / nuclear speck / neuron projection / membrane raft / axon / negative regulation of gene expression / neuronal cell body / dendrite / DNA damage response / protein kinase binding / enzyme binding / mitochondrion / DNA binding Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
![]() | Zhang W / Falcon B / Murzin AG / Fan J / Crowther RA / Goedert M / Scheres SHW | |||||||||
![]() | ![]() Title: Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer's and Pick's diseases. Authors: Wenjuan Zhang / Benjamin Falcon / Alexey G Murzin / Juan Fan / R Anthony Crowther / Michel Goedert / Sjors Hw Scheres / ![]() Abstract: Assembly of microtubule-associated protein tau into filamentous inclusions underlies a range of neurodegenerative diseases. Tau filaments adopt different conformations in Alzheimer's and Pick's ...Assembly of microtubule-associated protein tau into filamentous inclusions underlies a range of neurodegenerative diseases. Tau filaments adopt different conformations in Alzheimer's and Pick's diseases. Here, we used cryo- and immuno- electron microscopy to characterise filaments that were assembled from recombinant full-length human tau with four (2N4R) or three (2N3R) microtubule-binding repeats in the presence of heparin. 2N4R tau assembles into multiple types of filaments, and the structures of three types reveal similar 'kinked hairpin' folds, in which the second and third repeats pack against each other. 2N3R tau filaments are structurally homogeneous, and adopt a dimeric core, where the third repeats of two tau molecules pack in a parallel manner. The heparin-induced tau filaments differ from those of Alzheimer's or Pick's disease, which have larger cores with different repeat compositions. Our results illustrate the structural versatility of amyloid filaments, and raise questions about the relevance of in vitro assembly. | |||||||||
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 | ![]() | 12.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.1 KB 19.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.1 KB | Display | ![]() |
Images | ![]() | 25.7 KB | ||
Masks | ![]() | 64 MB | ![]() | |
Others | ![]() ![]() | 49.3 MB 49.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6qjpMC ![]() 4563C ![]() 4564C ![]() 4566C ![]() 6qjhC ![]() 6qjmC ![]() 6qjqC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data size: 446.3 / Data #1: Aligned micrographs [micrographs - single frame] / Data #2: Raw movies [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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Annotation | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.38 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | ![]() | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: Half map of helical reconstruction of heparin-induced 2N4R...
File | emd_4565_half_map_1.map | ||||||||||||
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Annotation | Half map of helical reconstruction of heparin-induced 2N4R tau jagged filaments | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: The other half map of helical reconstruction of...
File | emd_4565_half_map_2.map | ||||||||||||
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Annotation | The other half map of helical reconstruction of heparin-induced 2N4R tau jagged filaments | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : heparin-induced 2N4R tau jagged filaments
Entire | Name: heparin-induced 2N4R tau jagged filaments |
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Components |
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-Supramolecule #1: heparin-induced 2N4R tau jagged filaments
Supramolecule | Name: heparin-induced 2N4R tau jagged filaments / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all Details: Recombinant 2N4R tau protein was induced into filaments by adding heparin |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
Molecular weight | Theoretical: 45.85 kDa/nm |
-Macromolecule #1: Isoform Tau-F of Microtubule-associated protein tau
Macromolecule | Name: Isoform Tau-F of Microtubule-associated protein tau / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKST PTAEDVTAPL VDEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA G HVTQARMV SKSKDGTGSD DKKAKGADGK TKIATPRGAA PPGQKGQANA ...String: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKST PTAEDVTAPL VDEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA G HVTQARMV SKSKDGTGSD DKKAKGADGK TKIATPRGAA PPGQKGQANA TRIPAKTPPA PK TPPSSGE PPKSGDRSGY SSPGSPGTPG SRSRTPSLPT PPTREPKKVA VVRTPPKSPS SAK SRLQTA PVPMPDLKNV KSKIGSTENL KHQPGGGKVQ IINKKLDLSN VQSKCGSKDN IKHV PGGGS VQIVYKPVDL SKVTSKCGSL GNIHHKPGGG QVEVKSEKLD FKDRVQSKIG SLDNI THVP GGGNKKIETH KLTFRENAKA KTDHGAEIVY KSPVVSGDTS PRHLSNVSST GSIDMV DSP QLATLADEVS ASLAKQGL |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | helical reconstruction |
Aggregation state | filament |
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Sample preparation
Concentration | 2.0 mg/mL | |||||||||
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Buffer | pH: 7.4 Component:
Details: 20 mM Tris, pH 7.4, 100mM NaCl | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV / Details: Blot force: -12 ; Blot time: 4s. | |||||||||
Details | Recombinant tau protein was induced into filaments by incubation with heparin at 37 degree celsius for 3 days |
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Electron microscopy
Microscope | FEI POLARA 300 |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: INTEGRATING / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Digitization - Sampling interval: 14.0 µm / Number grids imaged: 1 / Number real images: 717 / Average exposure time: 1.0 sec. / Average electron dose: 48.0 e/Å2 Details: Images were collected in movie-mode at 30 frames per second |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.0 mm / Nominal defocus max: 2.8 µm / Nominal defocus min: 1.7 µm |
Sample stage | Specimen holder model: GATAN LIQUID NITROGEN / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Tecnai Polara / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Details | A stack of three consecutive monomers was refined to preserve nearest-neighbour interactions for the middle chain. Side-chain clashes were detected using MOLPROBITY, and corrected by iterative cycles of real-space refinement in COOT and Fourier-space refinement in REFMAC and PHENIX. For each refined structure, separate model refinements were performed against a single half-map, and the resulting model was compared to the other half-map to confirm the absence of overfitting. |
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Refinement | Space: RECIPROCAL / Protocol: AB INITIO MODEL / Overall B value: 33.2 / Target criteria: Fourier shell correlation |
Output model | ![]() PDB-6qjp: |