|Entry||Database: EMDB / ID: 3918|
|Title||Recombinant human Bri2 BRICHOS domain, oligomeric state|
|Map data||Negative stain 3D density map of the Bri2 Brichos domain in its oligomeric state, Molecular wieght, 370 kDaMethod: Single particle TEM|
|Sample||Oligomeric Bri2 BRICHOS|
|Source||Homo sapiens / / human|
|Method||Negative stain / single particle reconstruction / 16.5 Å resolution|
|Authors||Hebert H / Johansson J / Nilsson HE / Koeck PJB / Chen G|
|Citation||Journal: Nat Commun / Year: 2017|
Title: Bri2 BRICHOS client specificity and chaperone activity are governed by assembly state.
Authors: Gefei Chen / Axel Abelein / Harriet E Nilsson / Axel Leppert / Yuniesky Andrade-Talavera / Simone Tambaro / Lovisa Hemmingsson / Firoz Roshan / Michael Landreh / Henrik Biverstål / Philip J B Koeck / Jenny Presto / Hans Hebert / André Fisahn / Jan Johansson
Abstract: Protein misfolding and aggregation is increasingly being recognized as a cause of disease. In Alzheimer's disease the amyloid-β peptide (Aβ) misfolds into neurotoxic oligomers and assembles into ...Protein misfolding and aggregation is increasingly being recognized as a cause of disease. In Alzheimer's disease the amyloid-β peptide (Aβ) misfolds into neurotoxic oligomers and assembles into amyloid fibrils. The Bri2 protein associated with Familial British and Danish dementias contains a BRICHOS domain, which reduces Aβ fibrillization as well as neurotoxicity in vitro and in a Drosophila model, but also rescues proteins from irreversible non-fibrillar aggregation. How these different activities are mediated is not known. Here we show that Bri2 BRICHOS monomers potently prevent neuronal network toxicity of Aβ, while dimers strongly suppress Aβ fibril formation. The dimers assemble into high-molecular-weight oligomers with an apparent two-fold symmetry, which are efficient inhibitors of non-fibrillar protein aggregation. These results indicate that Bri2 BRICHOS affects qualitatively different aspects of protein misfolding and toxicity via different quaternary structures, suggesting a means to generate molecular chaperone diversity.
|Date||Deposition: Oct 12, 2017 / Header (metadata) release: Dec 20, 2017 / Map release: Dec 27, 2017 / Last update: Dec 27, 2017|
Downloads & links
|File||emd_3918.map.gz (map file in CCP4 format, 4500 KB)|
|Projections & slices|
Images are generated by Spider package.
|Voxel size||X=Y=Z: 2.076 Å|
CCP4 map header:
-Entire Oligomeric Bri2 BRICHOS
|Entire||Name: Oligomeric Bri2 BRICHOS / Number of components: 2|
|Mass||Experimental: 370 kDa|
-Component #1: cellular-component, Oligomeric Bri2 BRICHOS
|Cellular-component||Name: Oligomeric Bri2 BRICHOS / Recombinant expression: No|
|Mass||Experimental: 370 kDa|
|Source||Species: Homo sapiens / / human|
|Source (engineered)||Expression System: Escherichia coli / / bacteria / / Vector: pET / Strain: Shuttle T7|
-Component #2: protein, Bri2 BRICHOS domain
|Protein||Name: Bri2 BRICHOS domain / Recombinant expression: No|
|Source (engineered)||Expression System: Homo sapiens / / human / Strain: Human|
|Specimen||Specimen state: particle / Method: Negative stain|
|Sample solution||Specimen conc.: 0.047 mg/ml / pH: 8|
|Staining||2% Uranyl Acetate|
|Vitrification||Cryogen name: NONE|
-Electron microscopy imaging
|Imaging||Microscope: JEOL 2100F / Details: per frame =1.44 e/A2|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Electron dose: 57.5 e/Å2 / Illumination mode: FLOOD BEAM|
|Lens||Magnification: 60000 X (nominal), 61680 X (calibrated) / Cs: 2 mm / Imaging mode: BRIGHT FIELD|
|Specimen Holder||Model: JEOL|
|Image acquisition||Number of digital images: 24|
Details: Negative stain images were collected in movie-mode at 20 frames per second. For each exposure, the comprised frames were drift corrected using the DE_process_frames-2.7.1.py script
|Processing||Method: single particle reconstruction / Applied symmetry: D2 (2*2 fold dihedral) / Number of projections: 2718|
|3D reconstruction||Algorithm: FOURIER SPACE / Software: EMAN2|
CTF correction: For low resolution data EMAN2 use a 1D structure factor during the CTF procedure
Resolution: 16.5 Å / Resolution method: FSC 0.143 CUT-OFF
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