+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | In vitro assembled 297-394 tau filaments, 700 rpm (34b) | |||||||||
![]() | Sharpened map of in vitro assembled 297-394 tau filaments, 700 rpm (34b) | |||||||||
![]() |
| |||||||||
![]() | Alzheimer's Disease / Amyloid / Tau / Neurodegeneration / PROTEIN FIBRIL | |||||||||
Function / homology | ![]() plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / microtubule lateral binding / axonal transport / positive regulation of protein localization to synapse / main axon / phosphatidylinositol bisphosphate binding / tubulin complex ...plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / microtubule lateral binding / axonal transport / positive regulation of protein localization to synapse / main axon / phosphatidylinositol bisphosphate binding / tubulin complex / regulation of long-term synaptic depression / negative regulation of tubulin deacetylation / generation of neurons / regulation of chromosome organization / rRNA metabolic process / axonal transport of mitochondrion / regulation of mitochondrial fission / axon development / central nervous system neuron development / intracellular distribution of mitochondria / regulation of microtubule polymerization / microtubule polymerization / lipoprotein particle binding / minor groove of adenine-thymine-rich DNA binding / dynactin binding / negative regulation of mitochondrial membrane potential / apolipoprotein binding / glial cell projection / axolemma / protein polymerization / negative regulation of mitochondrial fission / Caspase-mediated cleavage of cytoskeletal proteins / regulation of microtubule polymerization or depolymerization / positive regulation of axon extension / neurofibrillary tangle assembly / Activation of AMPK downstream of NMDARs / synapse assembly / regulation of cellular response to heat / supramolecular fiber organization / positive regulation of protein localization / regulation of calcium-mediated signaling / somatodendritic compartment / cellular response to brain-derived neurotrophic factor stimulus / cytoplasmic microtubule organization / axon cytoplasm / positive regulation of microtubule polymerization / stress granule assembly / phosphatidylinositol binding / regulation of microtubule cytoskeleton organization / nuclear periphery / protein phosphatase 2A binding / positive regulation of superoxide anion generation / cellular response to reactive oxygen species / astrocyte activation / Hsp90 protein binding / microglial cell activation / cellular response to nerve growth factor stimulus / synapse organization / response to lead ion / PKR-mediated signaling / regulation of synaptic plasticity / protein homooligomerization / regulation of autophagy / SH3 domain binding / memory / microtubule cytoskeleton organization / cytoplasmic ribonucleoprotein granule / neuron projection development / cell-cell signaling / single-stranded DNA binding / microtubule cytoskeleton / protein-folding chaperone binding / actin binding / cellular response to heat / cell body / growth cone / double-stranded DNA binding / microtubule binding / protein-macromolecule adaptor activity / dendritic spine / sequence-specific DNA binding / amyloid fibril formation / microtubule / learning or memory / neuron projection / nuclear speck / membrane raft / axon / negative regulation of gene expression / neuronal cell body / dendrite / DNA damage response / protein kinase binding / enzyme binding / mitochondrion / DNA binding / RNA binding / extracellular region / identical protein binding / nucleus Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 2.99 Å | |||||||||
![]() | Lovestam S / Scheres SHW | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: Assembly of recombinant tau into filaments identical to those of Alzheimer's disease and chronic traumatic encephalopathy. Authors: Sofia Lövestam / Fujiet Adrian Koh / Bart van Knippenberg / Abhay Kotecha / Alexey G Murzin / Michel Goedert / Sjors H W Scheres / ![]() ![]() Abstract: Abundant filamentous inclusions of tau are characteristic of more than 20 neurodegenerative diseases that are collectively termed tauopathies. Electron cryo-microscopy (cryo-EM) structures of tau ...Abundant filamentous inclusions of tau are characteristic of more than 20 neurodegenerative diseases that are collectively termed tauopathies. Electron cryo-microscopy (cryo-EM) structures of tau amyloid filaments from human brain revealed that distinct tau folds characterise many different diseases. A lack of laboratory-based model systems to generate these structures has hampered efforts to uncover the molecular mechanisms that underlie tauopathies. Here, we report in vitro assembly conditions with recombinant tau that replicate the structures of filaments from both Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE), as determined by cryo-EM. Our results suggest that post-translational modifications of tau modulate filament assembly, and that previously observed additional densities in AD and CTE filaments may arise from the presence of inorganic salts, like phosphates and sodium chloride. In vitro assembly of tau into disease-relevant filaments will facilitate studies to determine their roles in different diseases, as well as the development of compounds that specifically bind to these structures or prevent their formation. | |||||||||
History |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 23 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 16.2 KB 16.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.1 KB | Display | ![]() |
Images | ![]() | 59.5 KB | ||
Filedesc metadata | ![]() | 5.4 KB | ||
Others | ![]() ![]() ![]() | 48 MB 48.2 MB 48.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1 MB | Display | |
Data in XML | ![]() | 16.2 KB | Display | |
Data in CIF | ![]() | 21.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7qjxMC ![]() 7qjvC ![]() 7qjwC ![]() 7qjyC ![]() 7qjzC ![]() 7qk1C ![]() 7qk2C ![]() 7qk3C ![]() 7qk5C ![]() 7qk6C ![]() 7qkfC ![]() 7qkgC ![]() 7qkhC ![]() 7qkiC ![]() 7qkjC ![]() 7qkkC ![]() 7qklC ![]() 7qkmC ![]() 7qkuC ![]() 7qkvC ![]() 7qkwC ![]() 7qkxC ![]() 7qkyC ![]() 7qkzC ![]() 7ql0C ![]() 7ql1C ![]() 7ql2C ![]() 7ql3C ![]() 7ql4C ![]() 7r4tC ![]() 7r5hC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Sharpened map of in vitro assembled 297-394 tau filaments, 700 rpm (34b) | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Additional map: Map of in vitro assembled 297-394 tau filaments, 700 rpm (34b)
File | emd_14025_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Map of in vitro assembled 297-394 tau filaments, 700 rpm (34b) | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half map 1 of in vitro assembled 297-394 tau filaments, 700 rpm (34b)
File | emd_14025_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half map 1 of in vitro assembled 297-394 tau filaments, 700 rpm (34b) | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half map 2 of in vitro assembled 297-394 tau filaments, 700 rpm (34b)
File | emd_14025_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half map 2 of in vitro assembled 297-394 tau filaments, 700 rpm (34b) | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : Tau
Entire | Name: Tau |
---|---|
Components |
|
-Supramolecule #1: Tau
Supramolecule | Name: Tau / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: ![]() |
-Macromolecule #1: Microtubule-associated protein tau
Macromolecule | Name: Microtubule-associated protein tau / type: protein_or_peptide / ID: 1 / Number of copies: 12 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 45.919871 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKSTP TAEDVTAPLV DEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA GHVTQARMVS KSKDGTGSDD KKAKGADGKT KIATPRGAAP P GQKGQANA ...String: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKSTP TAEDVTAPLV DEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA GHVTQARMVS KSKDGTGSDD KKAKGADGKT KIATPRGAAP P GQKGQANA TRIPAKTPPA PKTPPSSGEP PKSGDRSGYS SPGSPGTPGS RSRTPSLPTP PTREPKKVAV VRTPPKSPSS AK SRLQTAP VPMPDLKNVK SKIGSTENLK HQPGGGKVQI INKKLDLSNV QSKCGSKDNI KHVPGGGSVQ IVYKPVDLSK VTS KCGSLG NIHHKPGGGQ VEVKSEKLDF KDRVQSKIGS LDNITHVPGG GNKKIETHKL TFRENAKAKT DHGAEIVYKS PVVS GDTSP RHLSNVSSTG SIDMVDSPQL ATLADEVSAS LAKQGL UniProtKB: Microtubule-associated protein tau |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | helical reconstruction |
Aggregation state | filament |
-
Sample preparation
Buffer | pH: 7.4 |
---|---|
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
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: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.5 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
-
Image processing
-Atomic model buiding 1
Refinement | Protocol: AB INITIO MODEL |
---|---|
Output model | ![]() PDB-7qjx: |