+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Tau SF subtomogram average relating to LOL2_SF Figure 4i-j | |||||||||
![]() | ||||||||||
![]() |
| |||||||||
![]() | Amyloid / Filament / Alzheimer's / helical / PROTEIN FIBRIL | |||||||||
Biological species | ![]() | |||||||||
Method | subtomogram averaging / cryo EM / Resolution: 19.0 Å | |||||||||
![]() | Jenkins J | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: CryoET of β-amyloid and tau within postmortem Alzheimer's disease brain. Authors: Madeleine A G Gilbert / Nayab Fatima / Joshua Jenkins / Thomas J O'Sullivan / Andreas Schertel / Yehuda Halfon / Martin Wilkinson / Tjado H J Morrema / Mirjam Geibel / Randy J Read / Neil A ...Authors: Madeleine A G Gilbert / Nayab Fatima / Joshua Jenkins / Thomas J O'Sullivan / Andreas Schertel / Yehuda Halfon / Martin Wilkinson / Tjado H J Morrema / Mirjam Geibel / Randy J Read / Neil A Ranson / Sheena E Radford / Jeroen J M Hoozemans / René A W Frank / ![]() ![]() ![]() Abstract: A defining pathological feature of most neurodegenerative diseases is the assembly of proteins into amyloid that form disease-specific structures. In Alzheimer's disease, this is characterized by the ...A defining pathological feature of most neurodegenerative diseases is the assembly of proteins into amyloid that form disease-specific structures. In Alzheimer's disease, this is characterized by the deposition of β-amyloid and tau with disease-specific conformations. The in situ structure of amyloid in the human brain is unknown. Here, using cryo-fluorescence microscopy-targeted cryo-sectioning, cryo-focused ion beam-scanning electron microscopy lift-out and cryo-electron tomography, we determined in-tissue architectures of β-amyloid and tau pathology in a postmortem Alzheimer's disease donor brain. β-amyloid plaques contained a mixture of fibrils, some of which were branched, and protofilaments, arranged in parallel arrays and lattice-like structures. Extracellular vesicles and cuboidal particles defined the non-amyloid constituents of β-amyloid plaques. By contrast, tau inclusions formed parallel clusters of unbranched filaments. Subtomogram averaging a cluster of 136 tau filaments in a single tomogram revealed the polypeptide backbone conformation and filament polarity orientation of paired helical filaments within tissue. Filaments within most clusters were similar to each other, but were different between clusters, showing amyloid heterogeneity that is spatially organized by subcellular location. The in situ structural approaches outlined here for human donor tissues have applications to a broad range of neurodegenerative diseases. | |||||||||
History |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 3.1 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 16.4 KB 16.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 3.6 KB | Display | ![]() |
Images | ![]() | 19.3 KB | ||
Masks | ![]() | 3.4 MB | ![]() | |
Filedesc metadata | ![]() | 5.1 KB | ||
Others | ![]() ![]() | 2.4 MB 2.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 742.1 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 741.6 KB | Display | |
Data in XML | ![]() | 9.3 KB | Display | |
Data in CIF | ![]() | 12.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | C: citing same article ( |
---|
-
Links
EMDB pages | ![]() ![]() |
---|
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 2.38 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | ![]() | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_50162_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #2
File | emd_50162_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : Microtubule-associated protein tau
Entire | Name: Microtubule-associated protein tau |
---|---|
Components |
|
-Supramolecule #1: Microtubule-associated protein tau
Supramolecule | Name: Microtubule-associated protein tau / type: tissue / 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 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Sequence | String: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKST PTAEDVTAPL VDEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA G HVTQEPES GKVVQEGFLR EPGPPGLSHQ LMSGMPGAPL LPEGPREATR ...String: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKST PTAEDVTAPL VDEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA G HVTQEPES GKVVQEGFLR EPGPPGLSHQ LMSGMPGAPL LPEGPREATR QPSGTGPEDT EG GRHAPEL LKHQLLGDLH QEGPPLKGAG GKERPGSKEE VDEDRDVDES SPQDSPPSKA SPA QDGRPP QTAAREATSI PGFPAEGAIP LPVDFLSKVS TEIPASEPDG PSVGRAKGQD APLE FTFHV EITPNVQKEQ AHSEEHLGRA AFPGAPGEGP EARGPSLGED TKEADLPEPS EKQPA AAPR GKPVSRVPQL KARMVSKSKD GTGSDDKKAK TSTRSSAKTL KNRPCLSPKH PTPGSS DPL IQPSSPAVCP EPPSSPKYVS SVTSRTGSSG AKEMKLKGAD GKTKIATPRG AAPPGQK GQ ANATRIPAKT PPAPKTPPSS GEPPKSGDRS GYSSPGSPGT PGSRSRTPSL PTPPTREP K KVAVVRTPPK SPSSAKSRLQ TAPVPMPDLK NVKSKIGSTE NLKHQPGGGK VQIINKKLD LSNVQSKCGS KDNIKHVPGG GSVQIVYKPV DLSKVTSKCG SLGNIHHKPG GGQVEVKSEK LDFKDRVQS KIGSLDNITH VPGGGNKKIE THKLTFRENA KAKTDHGAEI VYKSPVVSGD T SPRHLSNV SSTGSIDMVD SPQLATLADE VSASLAKQGL |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | subtomogram averaging |
Aggregation state | tissue |
-
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: 2.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 6.5 µm / Nominal defocus min: 5.0 µm / Nominal magnification: 53000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |