|Entry||Database: EMDB / ID: 3851|
|Title||Near-atomic resolution fibril structure of complete amyloid-beta(1-42) by cryo-EM|
|Map data||The density map was sharpened by a B-factor of -50 Ang^2 and filtered to 3.5 Ang. This density map was used for model building and refinement.|
|Sample||Beta-amyloid protein 42 fibrilsAmyloid beta:|
Amyloid beta A4 protein
|Function / homology||Amyloid precursor protein (APP) copper-binding (CuBD) domain signature. / Pancreatic trypsin inhibitor Kunitz domain / Amyloidogenic glycoprotein, heparin-binding / Amyloidogenic glycoprotein, amyloid-beta peptide / Formyl peptide receptors bind formyl peptides and many other ligands / Amyloidogenic glycoprotein, copper-binding / The NLRP3 inflammasome / TAK1 activates NFkB by phosphorylation and activation of IKKs complex / Amyloidogenic glycoprotein / Amyloidogenic glycoprotein, extracellular ...Amyloid precursor protein (APP) copper-binding (CuBD) domain signature. / Pancreatic trypsin inhibitor Kunitz domain / Amyloidogenic glycoprotein, heparin-binding / Amyloidogenic glycoprotein, amyloid-beta peptide / Formyl peptide receptors bind formyl peptides and many other ligands / Amyloidogenic glycoprotein, copper-binding / The NLRP3 inflammasome / TAK1 activates NFkB by phosphorylation and activation of IKKs complex / Amyloidogenic glycoprotein / Amyloidogenic glycoprotein, extracellular / Pancreatic trypsin inhibitor (Kunitz) family profile. / Amyloidogenic glycoprotein, extracellular domain conserved site / Amyloid precursor protein (APP) E1 domain profile. / Amyloid precursor protein (APP) E2 domain profile. / Amyloid precursor protein (APP) intracellular domain signature. / Platelet degranulation / ECM proteoglycans / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / G alpha (q) signalling events / G alpha (i) signalling events / Beta-amyloid precursor protein C-terminal / PH-like domain superfamily / Amyloidogenic glycoprotein, intracellular domain, conserved site / Proteinase inhibitor I2, Kunitz, conserved site / Pancreatic trypsin inhibitor (Kunitz) family signature. / E2 domain of amyloid precursor protein / Copper-binding of amyloid precursor, CuBD / Beta-amyloid precursor protein C-terminus / Beta-amyloid peptide (beta-APP) / Amyloid A4 N-terminal heparin-binding / Kunitz/Bovine pancreatic trypsin inhibitor domain / Amyloid fiber formation / Amyloidogenic glycoprotein, amyloid-beta peptide superfamily / Lysosome Vesicle Biogenesis / Amyloidogenic glycoprotein, copper-binding domain superfamily / Amyloidogenic glycoprotein, heparin-binding domain superfamily / Advanced glycosylation endproduct receptor signaling / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / Pancreatic trypsin inhibitor Kunitz domain superfamily / Amyloidogenic glycoprotein, E2 domain / Amyloid-beta precursor protein / Post-translational protein phosphorylation / TRAF6 mediated NF-kB activation / E2 domain superfamily / positive regulation of protein import / amylin binding / amyloid-beta complex / regulation of acetylcholine-gated cation channel activity / positive regulation of G protein-coupled receptor internalization / positive regulation of cellular response to thapsigargin / positive regulation of cellular response to tunicamycin / heparan sulfate binding / positive regulation of 1-phosphatidylinositol-3-kinase activity / positive regulation of response to endoplasmic reticulum stress / regulation of response to calcium ion / membrane lipid catabolic process / endosome to plasma membrane transport vesicle / receptor activator activity / acetylcholine receptor activator activity / collateral sprouting in absence of injury / regulation of dendritic spine maintenance / cellular response to norepinephrine stimulus / lipoprotein particle / positive regulation of oxidative stress-induced neuron death / negative regulation of blood circulation / positive regulation of endothelin secretion / microglia development / growth cone lamellipodium / negative regulation of mitochondrion organization / mating behavior / regulation of amyloid fibril formation / protein trimerization / cellular process / regulation of epidermal growth factor-activated receptor activity / smooth endoplasmic reticulum calcium ion homeostasis / growth cone filopodium / regulation of spontaneous synaptic transmission / positive regulation of astrocyte activation / astrocyte projection / astrocyte activation involved in immune response / tumor necrosis factor production / synaptic growth at neuromuscular junction / axon midline choice point recognition / regulation of synapse structure or activity / positive regulation of interleukin-1 beta biosynthetic process / positive regulation of amyloid fibril formation / intermediate-density lipoprotein particle / PTB domain binding / modulation of excitatory postsynaptic potential / suckling behavior / positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process / Golgi-associated vesicle / neuron remodeling / activation of MAPKKK activity / positive regulation of G protein-coupled receptor signaling pathway / ciliary rootlet / peptidase activator activity / high-density lipoprotein particle / positive regulation of cell activation / main axon|
Function and homology information
|Source||Homo sapiens (human)|
|Method||helical reconstruction / cryo EM / 4 Å resolution|
|Authors||Gremer L / Schoelzel D / Schenk C / Reinartz E / Labahn J / Ravelli R / Tusche M / Lopez-Iglesias C / Hoyer W / Heise H / Willbold D / Schroeder GF|
|Citation||Journal: Science / Year: 2017|
Title: Fibril structure of amyloid-β(1-42) by cryo-electron microscopy.
Authors: Lothar Gremer / Daniel Schölzel / Carla Schenk / Elke Reinartz / Jörg Labahn / Raimond B G Ravelli / Markus Tusche / Carmen Lopez-Iglesias / Wolfgang Hoyer / Henrike Heise / Dieter Willbold / Gunnar F Schröder
Abstract: Amyloids are implicated in neurodegenerative diseases. Fibrillar aggregates of the amyloid-β protein (Aβ) are the main component of the senile plaques found in brains of Alzheimer's disease ...Amyloids are implicated in neurodegenerative diseases. Fibrillar aggregates of the amyloid-β protein (Aβ) are the main component of the senile plaques found in brains of Alzheimer's disease patients. We present the structure of an Aβ(1-42) fibril composed of two intertwined protofilaments determined by cryo-electron microscopy (cryo-EM) to 4.0-angstrom resolution, complemented by solid-state nuclear magnetic resonance experiments. The backbone of all 42 residues and nearly all side chains are well resolved in the EM density map, including the entire N terminus, which is part of the cross-β structure resulting in an overall "LS"-shaped topology of individual subunits. The dimer interface protects the hydrophobic C termini from the solvent. The characteristic staggering of the nonplanar subunits results in markedly different fibril ends, termed "groove" and "ridge," leading to different binding pathways on both fibril ends, which has implications for fibril growth.
|Validation Report||PDB-ID: 5oqv|
SummaryFull reportAbout validation report
|Date||Deposition: Aug 14, 2017 / Header (metadata) release: Sep 13, 2017 / Map release: Sep 13, 2017 / Last update: Oct 18, 2017|
|Structure viewer||EM map: |
Downloads & links
|File||emd_3851.map.gz (map file in CCP4 format, 40311 KB)|
|Projections & slices|
Images are generated by Spider.
|Voxel size||X=Y=Z: 0.935 Å|
CCP4 map header:
-Entire Beta-amyloid protein 42 fibrils
|Entire||Name: Beta-amyloid protein 42 fibrils / Number of components: 2|
-Component #1: protein, Beta-amyloid protein 42 fibrils
|Protein||Name: Beta-amyloid protein 42 fibrilsAmyloid beta / Recombinant expression: No|
|Source||Species: Homo sapiens (human)|
|Source (engineered)||Expression System: Escherichia coli (E. coli)|
-Component #2: protein, Amyloid beta A4 protein
|Protein||Name: Amyloid beta A4 protein / Number of Copies: 9 / Recombinant expression: No|
|Mass||Theoretical: 4.520087 kDa|
|Source||Species: Homo sapiens (human)|
|Source (engineered)||Expression System: Escherichia coli (E. coli)|
|Specimen||Specimen state: filament / Method: cryo EM|
|Helical parameters||Axial symmetry: C1 (asymmetric) / Delta z: 2.335 Å / Delta phi: -179.275 deg.|
|Sample solution||Buffer solution: in water / pH: 2|
|Vitrification||Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE|
Details: 2.5 microL sample was applied to the grid, blotted for 2.5 s before plunging..
-Electron microscopy imaging
Model: Talos Arctica / Image courtesy: FEI Company
|Imaging||Microscope: FEI TECNAI ARCTICA|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Electron dose: 24 e/Å2 / Illumination mode: FLOOD BEAM|
|Lens||Magnification: 110000.0 X (nominal) / Cs: 2.7 mm / Imaging mode: BRIGHT FIELD|
|Specimen Holder||Model: OTHER|
|Camera||Detector: FEI FALCON III (4k x 4k)|
|Image acquisition||Number of digital images: 2026|
-Atomic model buiding
|Modeling #1||Target criteria: Cross-correlation coefficient / Refinement space: REAL|
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