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- EMDB-17177: Ab typeII filament from Guam ALS/PDC -

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Basic information

Entry
Database: EMDB / ID: EMD-17177
TitleAb typeII filament from Guam ALS/PDC
Map data
Sample
  • Complex: Ab typeII filaments from Guam ALS/PDC
    • Protein or peptide: Amyloid-beta precursor protein
KeywordsAb typeII filaments / Guam ALS/PDC / PROTEIN FIBRIL
Function / homology
Function and homology information


negative regulation of presynapse assembly / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / synaptic assembly at neuromuscular junction / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / axon midline choice point recognition ...negative regulation of presynapse assembly / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / synaptic assembly at neuromuscular junction / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / axon midline choice point recognition / smooth endoplasmic reticulum calcium ion homeostasis / astrocyte activation involved in immune response / NMDA selective glutamate receptor signaling pathway / mating behavior / regulation of spontaneous synaptic transmission / Golgi-associated vesicle / ciliary rootlet / PTB domain binding / Lysosome Vesicle Biogenesis / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / positive regulation of amyloid fibril formation / neuron remodeling / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / nuclear envelope lumen / COPII-coated ER to Golgi transport vesicle / suckling behavior / signaling receptor activator activity / dendrite development / modulation of excitatory postsynaptic potential / TRAF6 mediated NF-kB activation / presynaptic active zone / neuromuscular process controlling balance / The NLRP3 inflammasome / Advanced glycosylation endproduct receptor signaling / regulation of peptidyl-tyrosine phosphorylation / negative regulation of long-term synaptic potentiation / transition metal ion binding / regulation of presynapse assembly / regulation of multicellular organism growth / intracellular copper ion homeostasis / negative regulation of neuron differentiation / ECM proteoglycans / spindle midzone / positive regulation of T cell migration / smooth endoplasmic reticulum / Purinergic signaling in leishmaniasis infection / positive regulation of peptidyl-threonine phosphorylation / forebrain development / positive regulation of chemokine production / clathrin-coated pit / Notch signaling pathway / protein serine/threonine kinase binding / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of protein metabolic process / neuron projection maintenance / Mitochondrial protein degradation / extracellular matrix organization / response to interleukin-1 / ionotropic glutamate receptor signaling pathway / positive regulation of mitotic cell cycle / cholesterol metabolic process / axonogenesis / positive regulation of calcium-mediated signaling / positive regulation of peptidyl-serine phosphorylation / dendritic shaft / platelet alpha granule lumen / adult locomotory behavior / positive regulation of glycolytic process / central nervous system development / positive regulation of interleukin-1 beta production / learning / trans-Golgi network membrane / positive regulation of long-term synaptic potentiation / endosome lumen / locomotory behavior / astrocyte activation / Post-translational protein phosphorylation / positive regulation of JNK cascade / microglial cell activation / regulation of long-term neuronal synaptic plasticity / serine-type endopeptidase inhibitor activity / synapse organization / TAK1-dependent IKK and NF-kappa-B activation / positive regulation of non-canonical NF-kappaB signal transduction / visual learning / neuromuscular junction / recycling endosome / positive regulation of interleukin-6 production / Golgi lumen / cognition / neuron cellular homeostasis / positive regulation of inflammatory response / cellular response to amyloid-beta / endocytosis / neuron projection development / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / G2/M transition of mitotic cell cycle / positive regulation of tumor necrosis factor production / apical part of cell / synaptic vesicle
Similarity search - Function
Amyloidogenic glycoprotein, copper-binding / Amyloidogenic glycoprotein, copper-binding domain conserved site / Amyloidogenic glycoprotein, copper-binding domain superfamily / Copper-binding of amyloid precursor, CuBD / Amyloid precursor protein (APP) copper-binding (CuBD) domain signature. / Amyloidogenic glycoprotein, amyloid-beta peptide superfamily / Beta-amyloid peptide (beta-APP) / Amyloidogenic glycoprotein, amyloid-beta peptide / Beta-amyloid precursor protein C-terminal / Amyloidogenic glycoprotein, intracellular domain, conserved site ...Amyloidogenic glycoprotein, copper-binding / Amyloidogenic glycoprotein, copper-binding domain conserved site / Amyloidogenic glycoprotein, copper-binding domain superfamily / Copper-binding of amyloid precursor, CuBD / Amyloid precursor protein (APP) copper-binding (CuBD) domain signature. / Amyloidogenic glycoprotein, amyloid-beta peptide superfamily / Beta-amyloid peptide (beta-APP) / Amyloidogenic glycoprotein, amyloid-beta peptide / Beta-amyloid precursor protein C-terminal / Amyloidogenic glycoprotein, intracellular domain, conserved site / Beta-amyloid precursor protein C-terminus / Amyloid precursor protein (APP) intracellular domain signature. / Amyloidogenic glycoprotein, extracellular / Amyloidogenic glycoprotein, heparin-binding / Amyloidogenic glycoprotein, E2 domain / E2 domain superfamily / Amyloidogenic glycoprotein, heparin-binding domain superfamily / Amyloid A4 N-terminal heparin-binding / E2 domain of amyloid precursor protein / Amyloid precursor protein (APP) E1 domain profile. / Amyloid precursor protein (APP) E2 domain profile. / amyloid A4 / Amyloidogenic glycoprotein / Proteinase inhibitor I2, Kunitz, conserved site / Pancreatic trypsin inhibitor (Kunitz) family signature. / BPTI/Kunitz family of serine protease inhibitors. / Pancreatic trypsin inhibitor Kunitz domain / Kunitz/Bovine pancreatic trypsin inhibitor domain / Pancreatic trypsin inhibitor (Kunitz) family profile. / Pancreatic trypsin inhibitor Kunitz domain superfamily / PH-like domain superfamily
Similarity search - Domain/homology
Amyloid-beta precursor protein
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodhelical reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsQi C / Yang S / Scheres SHW / Goedert M
Funding support United Kingdom, 2 items
OrganizationGrant numberCountry
Medical Research Council (MRC, United Kingdom)MC_UP_A025_1013 United Kingdom
Medical Research Council (MRC, United Kingdom)MC_U105184291 United Kingdom
CitationJournal: Proc Natl Acad Sci U S A / Year: 2023
Title: Tau filaments from amyotrophic lateral sclerosis/parkinsonism-dementia complex adopt the CTE fold.
Authors: Chao Qi / Bert M Verheijen / Yasumasa Kokubo / Yang Shi / Stephan Tetter / Alexey G Murzin / Asa Nakahara / Satoru Morimoto / Marc Vermulst / Ryogen Sasaki / Eleonora Aronica / Yoshifumi ...Authors: Chao Qi / Bert M Verheijen / Yasumasa Kokubo / Yang Shi / Stephan Tetter / Alexey G Murzin / Asa Nakahara / Satoru Morimoto / Marc Vermulst / Ryogen Sasaki / Eleonora Aronica / Yoshifumi Hirokawa / Kiyomitsu Oyanagi / Akiyoshi Kakita / Benjamin Ryskeldi-Falcon / Mari Yoshida / Masato Hasegawa / Sjors H W Scheres / Michel Goedert /
Abstract: The amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of the island of Guam and the Kii peninsula of Japan is a fatal neurodegenerative disease of unknown cause that is ...The amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of the island of Guam and the Kii peninsula of Japan is a fatal neurodegenerative disease of unknown cause that is characterized by the presence of abundant filamentous tau inclusions in brains and spinal cords. Here, we used electron cryo-microscopy to determine the structures of tau filaments from the cerebral cortex of three cases of ALS/PDC from Guam and eight cases from Kii, as well as from the spinal cord of two of the Guam cases. Tau filaments had the chronic traumatic encephalopathy (CTE) fold, with variable amounts of Type I and Type II filaments. Paired helical tau filaments were also found in three Kii cases and tau filaments with the corticobasal degeneration fold in one Kii case. We identified a new Type III CTE tau filament, where protofilaments pack against each other in an antiparallel fashion. ALS/PDC is the third known tauopathy with CTE-type filaments and abundant tau inclusions in cortical layers II/III, the others being CTE and subacute sclerosing panencephalitis. Because these tauopathies are believed to have environmental causes, our findings support the hypothesis that ALS/PDC is caused by exogenous factors.
History
DepositionApr 20, 2023-
Header (metadata) releaseMar 27, 2024-
Map releaseMar 27, 2024-
UpdateMar 27, 2024-
Current statusMar 27, 2024Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_17177.png

Downloads & links

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Map

FileDownload / File: emd_17177.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
0.82 Å/pix.
x 400 pix.
= 329.6 Å		0.82 Å/pix.
x 400 pix.
= 329.6 Å		0.82 Å/pix.
x 400 pix.
= 329.6 Å

Surface

Projections

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.824 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.004
Minimum - Maximum-0.008632894 - 0.01808857
Average (Standard dev.)0.000025211097 (±0.000700984)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 329.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_17177_msk_1.map
Projections & Slices
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Half map: #1

Fileemd_17177_half_map_1.map
Projections & Slices
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Histogram

Histogram (log scale)

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Half map: #2

Fileemd_17177_half_map_2.map
Projections & Slices
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Sample components

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Entire : Ab typeII filaments from Guam ALS/PDC

EntireName: Ab typeII filaments from Guam ALS/PDC
Components
  • Complex: Ab typeII filaments from Guam ALS/PDC
    • Protein or peptide: Amyloid-beta precursor protein

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Supramolecule #1: Ab typeII filaments from Guam ALS/PDC

SupramoleculeName: Ab typeII filaments from Guam ALS/PDC / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Amyloid-beta precursor protein

MacromoleculeName: Amyloid-beta precursor protein / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 87.046219 KDa
SequenceString: MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK TCIDTKEGIL QYCQEVYPEL QITNVVEAN QPVTIQNWCK RGRKQCKTHP HFVIPYRCLV GEFVSDALLV PDKCKFLHQE RMDVCETHLH WHTVAKETCS E KSTNLHDY ...String:
MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK TCIDTKEGIL QYCQEVYPEL QITNVVEAN QPVTIQNWCK RGRKQCKTHP HFVIPYRCLV GEFVSDALLV PDKCKFLHQE RMDVCETHLH WHTVAKETCS E KSTNLHDY GMLLPCGIDK FRGVEFVCCP LAEESDNVDS ADAEEDDSDV WWGGADTDYA DGSEDKVVEV AEEEEVAEVE EE EADDDED DEDGDEVEEE AEEPYEEATE RTTSIATTTT TTTESVEEVV REVCSEQAET GPCRAMISRW YFDVTEGKCA PFF YGGCGG NRNNFDTEEY CMAVCGSAMS QSLLKTTQEP LARDPVKLPT TAASTPDAVD KYLETPGDEN EHAHFQKAKE RLEA KHRER MSQVMREWEE AERQAKNLPK ADKKAVIQHF QEKVESLEQE AANERQQLVE THMARVEAML NDRRRLALEN YITAL QAVP PRPRHVFNML KKYVRAEQKD RQHTLKHFEH VRMVDPKKAA QIRSQVMTHL RVIYERMNQS LSLLYNVPAV AEEIQD EVD ELLQKEQNYS DDVLANMISE PRISYGNDAL MPSLTETKTT VELLPVNGEF SLDDLQPWHS FGADSVPANT ENEVEPV DA RPAADRGLTT RPGSGLTNIK TEEISEVKMD AEFRHDSGYE VHHQKLVFFA EDVGSNKGAI IGLMVGGVVI ATVIVITL V MLKKKQYTSI HHGVVEVDAA VTPEERHLSK MQQNGYENPT YKFFEQMQN

UniProtKB: Amyloid-beta precursor protein

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Experimental details

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Structure determination

Methodcryo EM
Processinghelical reconstruction
Aggregation statefilament

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Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

DetailsAb typeII filament from Guam ALS/PDC
Final reconstructionApplied symmetry - Helical parameters - Δz: 4.79 Å
Applied symmetry - Helical parameters - Δ&Phi: -2.99 °
Applied symmetry - Helical parameters - Axial symmetry: C2 (2 fold cyclic)
Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 20363
Startup modelType of model: INSILICO MODEL
Final angle assignmentType: NOT APPLICABLE
FSC plot (resolution estimation)

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