|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 fibrils:|
Amyloid beta A4 protein
|Function / homology||Platelet degranulation / Amyloidogenic glycoprotein / Amyloidogenic glycoprotein, extracellular domain conserved site / ECM proteoglycans / Advanced glycosylation endproduct receptor signaling / The NLRP3 inflammasome / Amyloidogenic glycoprotein, heparin-binding / Amyloidogenic glycoprotein, amyloid-beta peptide / PH-like domain superfamily / Amyloidogenic glycoprotein, copper-binding ...Platelet degranulation / Amyloidogenic glycoprotein / Amyloidogenic glycoprotein, extracellular domain conserved site / ECM proteoglycans / Advanced glycosylation endproduct receptor signaling / The NLRP3 inflammasome / Amyloidogenic glycoprotein, heparin-binding / Amyloidogenic glycoprotein, amyloid-beta peptide / PH-like domain superfamily / Amyloidogenic glycoprotein, copper-binding / Amyloidogenic glycoprotein, extracellular / Proteinase inhibitor I2, Kunitz, conserved site / Pancreatic trypsin inhibitor Kunitz domain / Lysosome Vesicle Biogenesis / Formyl peptide receptors bind formyl peptides and many other ligands / TAK1 activates NFkB by phosphorylation and activation of IKKs complex / G alpha (i) signalling events / G alpha (q) signalling events / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / RIP-mediated NFkB activation via ZBP1 / DEx/H-box helicases activate type I IFN and inflammatory cytokines production / Amyloidogenic glycoprotein, intracellular domain, conserved site / Beta-amyloid precursor protein C-terminal / Amyloidogenic glycoprotein, E2 domain / Beta-amyloid peptide (beta-APP) / Pancreatic trypsin inhibitor (Kunitz) family profile. / Amyloidogenic glycoprotein intracellular domain signature. / Amyloidogenic glycoprotein extracellular domain signature. / Pancreatic trypsin inhibitor (Kunitz) family signature. / E2 domain of amyloid precursor protein / Amyloid beta A4 protein / beta-amyloid precursor protein C-terminus / Amyloid fiber formation / Copper-binding of amyloid precursor, CuBD / Amyloid A4 N-terminal heparin-binding / Amyloidogenic glycoprotein, copper-binding domain superfamily / Amyloidogenic glycoprotein, amyloid-beta peptide superfamily / Pancreatic trypsin inhibitor Kunitz domain superfamily / TRAF6 mediated NF-kB activation / Post-translational protein phosphorylation / E2 domain superfamily / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / Kunitz/Bovine pancreatic trypsin inhibitor domain / Amyloidogenic glycoprotein, heparin-binding domain superfamily / amylin binding / regulation of acetylcholine-gated cation channel activity / positive regulation of protein import / positive regulation of G-protein coupled receptor internalization / positive regulation of cellular response to thapsigargin / positive regulation of cellular response to tunicamycin / positive regulation of 1-phosphatidylinositol-3-kinase activity / heparan sulfate binding / positive regulation of response to endoplasmic reticulum stress / receptor activator activity / regulation of response to calcium ion / acetylcholine receptor activator activity / regulation of dendritic spine maintenance / collateral sprouting in absence of injury / endosome to plasma membrane transport vesicle / cellular response to norepinephrine stimulus / lipoprotein particle / synaptic growth at neuromuscular junction / positive regulation of oxidative stress-induced neuron death / microglia development / growth cone lamellipodium / negative regulation of mitochondrion organization / mating behavior / regulation of synapse structure or activity / regulation of amyloid fibril formation / astrocyte projection / smooth endoplasmic reticulum calcium ion homeostasis / protein trimerization / main axon / regulation of epidermal growth factor-activated receptor activity / growth cone filopodium / regulation of spontaneous synaptic transmission / axo-dendritic transport / tumor necrosis factor production / axon midline choice point recognition / astrocyte activation involved in immune response / positive regulation of astrocyte activation / intermediate-density lipoprotein particle / cellular process / positive regulation of amyloid fibril formation / PTB domain binding / positive regulation of cAMP metabolic process / modulation of excitatory postsynaptic potential / positive regulation of microglial cell activation / neuron remodeling / amyloid-beta complex / activation of MAPKKK activity / positive regulation of G-protein coupled receptor protein signaling pathway / positive regulation of amyloid-beta formation / ciliary rootlet / positive regulation of cell activation / high-density lipoprotein particle / lipoprotein metabolic process / peptidase activator activity / suckling behavior / negative regulation of protein localization to nucleus|
Function and homology information
|Source||Homo sapiens (human)|
|Method||helical reconstruction / cryo EM / 4 Å resolution|
|Authors||Gremer L / Schoelzel D|
|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.
Copyright: 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
|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 fibrils / 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 / Recombinant expression: No|
|Mass||Theoretical: 4.520087 kDa|
|Source (engineered)||Expression System: Homo sapiens (human)|
|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 X (nominal) / Cs: 2.7 mm / Imaging mode: BRIGHT FIELD|
|Specimen Holder||Model: OTHER|
|Image acquisition||Number of digital images: 2026|
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