PDB-8otf: Ab typeII filament from Guam ALS/PDC

Basic information

• Entry: Database: PDB / ID: 8otf
• Title: Ab typeII filament from Guam ALS/PDC
• Components: Amyloid-beta precursor protein
• Keywords: PROTEIN FIBRIL / Ab typeII filaments / Guam ALS/PDC

Function / homology

Function:

amyloid-beta complex / growth cone lamellipodium / cellular response to norepinephrine stimulus / growth cone filopodium / microglia development / collateral sprouting in absence of injury / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / regulation of Wnt signaling pathway / regulation of synapse structure or activity / axon midline choice point recognition / astrocyte activation involved in immune response / NMDA selective glutamate receptor signaling pathway / regulation of spontaneous synaptic transmission / mating behavior / growth factor receptor binding / peptidase activator activity / Golgi-associated vesicle / PTB domain binding / positive regulation of amyloid fibril formation / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / astrocyte projection / Lysosome Vesicle Biogenesis / neuron remodeling / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / nuclear envelope lumen / dendrite development / positive regulation of protein metabolic process / TRAF6 mediated NF-kB activation / signaling receptor activator activity / Advanced glycosylation endproduct receptor signaling / negative regulation of long-term synaptic potentiation / modulation of excitatory postsynaptic potential / The NLRP3 inflammasome / main axon / transition metal ion binding / intracellular copper ion homeostasis / regulation of multicellular organism growth / ECM proteoglycans / regulation of presynapse assembly / positive regulation of T cell migration / neuronal dense core vesicle / Purinergic signaling in leishmaniasis infection / positive regulation of chemokine production / cellular response to manganese ion / Notch signaling pathway / clathrin-coated pit / extracellular matrix organization / neuron projection maintenance / astrocyte activation / ionotropic glutamate receptor signaling pathway / Mitochondrial protein degradation / positive regulation of calcium-mediated signaling / positive regulation of mitotic cell cycle / axonogenesis / protein serine/threonine kinase binding / response to interleukin-1 / platelet alpha granule lumen / cellular response to copper ion / cellular response to cAMP / positive regulation of glycolytic process / central nervous system development / positive regulation of interleukin-1 beta production / dendritic shaft / endosome lumen / trans-Golgi network membrane / positive regulation of long-term synaptic potentiation / adult locomotory behavior / learning / positive regulation of JNK cascade / Post-translational protein phosphorylation / locomotory behavior / serine-type endopeptidase inhibitor activity / microglial cell activation / positive regulation of non-canonical NF-kappaB signal transduction / TAK1-dependent IKK and NF-kappa-B activation / cellular response to nerve growth factor stimulus / regulation of long-term neuronal synaptic plasticity / recycling endosome / synapse organization / visual learning / response to lead ion / positive regulation of interleukin-6 production / Golgi lumen / cognition / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / endocytosis / cellular response to amyloid-beta / neuron projection development / positive regulation of inflammatory response / positive regulation of tumor necrosis factor production / Platelet degranulation / heparin binding / regulation of translation / regulation of gene expression / early endosome membrane / G alpha (i) signalling events / perikaryon / G alpha (q) signalling events / dendritic spine

Domain/homology:

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

Component:

Amyloid-beta precursor protein

• Biological species: Homo sapiens (human)
• Method: ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.3 Å
• Authors: Qi, C. / Yang, S. / Scheres, S.H.W. / Goedert, M.

Funding support

United Kingdom, 2items

Organization	Grant number	Country
Medical Research Council (MRC, United Kingdom)	MC_UP_A025_1013	United Kingdom
Medical Research Council (MRC, United Kingdom)	MC_U105184291	United Kingdom

• Citation: Journal: 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 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 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

Deposition	Apr 20, 2023	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Mar 27, 2024	Provider: repository / Type: Initial release

Assembly

Deposited unit

A: Amyloid-beta precursor protein

B: Amyloid-beta precursor protein

C: Amyloid-beta precursor protein

D: Amyloid-beta precursor protein

E: Amyloid-beta precursor protein

F: Amyloid-beta precursor protein

Summary:

• 522 kDa, 6 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	522,277	6
Polymers	522,277	6
Non-polymers	0	0
Water	0	0

1

Summary:

• Idetical with deposited unit
• defined by author
• Evidence: electron microscopy

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555		1

Components

#1: Protein

A B C D E F
Amyloid-beta precursor protein / APP / ABPP / APPI / Alzheimer disease amyloid A4 protein homolog / Alzheimer disease amyloid protein / Amyloid precursor protein / Amyloid-beta (A4) precursor protein / Amyloid-beta A4 protein / Cerebral vascular amyloid peptide / CVAP / PreA4 / Protease nexin-II / PN-II

Details:

Mass: 87046.219 Da / Num. of mol.: 6 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P05067

Experimental details

Experiment

• Experiment: Method: ELECTRON MICROSCOPY
• EM experiment: Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction

Sample preparation

• Component: Name: Ab typeII filaments from Guam ALS/PDC / Type: COMPLEX / Entity ID: all / Source: NATURAL
• Source (natural): Organism: Homo sapiens (human)
• Buffer solution: pH: 7.4
• Specimen: Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
• Vitrification: Cryogen name: ETHANE

Electron microscopy imaging

• Experimental equipment: Model: Titan Krios / Image courtesy: FEI Company
• Microscopy: Model: FEI TITAN KRIOS
• Electron gun: Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
• Electron lens: Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm
• Image recording: Electron dose: 40 e/Ų / Film or detector model: GATAN K3 (6k x 4k)

Processing

• Image processing: Details: Ab typeII filament from Guam ALS/PDC
• CTF correction: Type: NONE
• Helical symmerty: Angular rotation/subunit: -2.99 ° / Axial rise/subunit: 4.79 Å / Axial symmetry: C2
• 3D reconstruction: Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 20363 / Symmetry type: HELICAL