|Entry||Database: EMDB / ID: 8720|
|Title||VGSNKGAIIGL from Amyloid Beta determined by MicroED|
|Map data||VGSNKGAIIGL from Amyloid Beta|
|Sample||Fibrils of Amyloid Beta segment 24-34|
|Function/homology||positive regulation of G-protein coupled receptor internalization / positive regulation of 1-phosphatidylinositol-3-kinase activity / amylin binding / regulation of acetylcholine-gated cation channel activity / positive regulation of protein import / positive regulation of cellular response to thapsigargin / positive regulation of cellular response to tunicamycin / heparan sulfate binding / positive regulation of response to endoplasmic reticulum stress / receptor activator activity ...positive regulation of G-protein coupled receptor internalization / positive regulation of 1-phosphatidylinositol-3-kinase activity / amylin binding / regulation of acetylcholine-gated cation channel activity / positive regulation of protein import / positive regulation of cellular response to thapsigargin / positive regulation of cellular response to tunicamycin / heparan sulfate binding / positive regulation of response to endoplasmic reticulum stress / receptor activator activity / regulation of response to calcium ion / acetylcholine receptor activator activity / Amyloidogenic glycoprotein, amyloid-beta peptide / regulation of dendritic spine maintenance / Formyl peptide receptors bind formyl peptides and many other ligands / Amyloidogenic glycoprotein, amyloid-beta peptide superfamily / Amyloid beta A4 protein / collateral sprouting in absence of injury / endosome to plasma membrane transport vesicle / cellular response to norepinephrine stimulus / Amyloidogenic glycoprotein, intracellular domain, conserved site / Amyloidogenic glycoprotein intracellular domain signature. / lipoprotein particle / Beta-amyloid peptide (beta-APP) / Amyloidogenic glycoprotein, heparin-binding domain superfamily / synaptic growth at neuromuscular junction / positive regulation of oxidative stress-induced neuron death / Amyloidogenic glycoprotein extracellular domain signature. / Amyloidogenic glycoprotein, copper-binding domain superfamily / Amyloidogenic glycoprotein, E2 domain / Amyloidogenic glycoprotein, extracellular / Beta-amyloid precursor protein C-terminal / Amyloidogenic glycoprotein / Amyloidogenic glycoprotein, copper-binding / Amyloidogenic glycoprotein, extracellular domain conserved site / E2 domain superfamily / Amyloidogenic glycoprotein, heparin-binding / beta-amyloid precursor protein C-terminus / microglia development / growth cone lamellipodium / Amyloid A4 N-terminal heparin-binding / negative regulation of mitochondrion organization / Copper-binding of amyloid precursor, CuBD / mating behavior / regulation of synapse structure or activity / regulation of amyloid fibril formation / E2 domain of amyloid precursor protein / positive regulation of tau-protein kinase activity / protein trimerization / smooth endoplasmic reticulum calcium ion homeostasis / main axon / regulation of epidermal growth factor-activated receptor activity / growth cone filopodium / axo-dendritic transport / regulation of spontaneous synaptic transmission / tumor necrosis factor production / axon midline choice point recognition / astrocyte activation involved in immune response / positive regulation of astrocyte activation / astrocyte projection / 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 / positive regulation of amyloid-beta formation / activation of MAPKKK activity / positive regulation of G-protein coupled receptor protein signaling pathway / ciliary rootlet / DEx/H-box helicases activate type I IFN and inflammatory cytokines production / positive regulation of cell activation / Lysosome Vesicle Biogenesis / high-density lipoprotein particle / peptidase activator activity / lipoprotein metabolic process / suckling behavior / negative regulation of protein localization to nucleus / positive regulation of protein metabolic process / adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway / heparan sulfate proteoglycan binding / positive regulation of membrane protein ectodomain proteolysis / dendrite development / COPII-coated ER to Golgi transport vesicle / RIP-mediated NFkB activation via ZBP1 / The NLRP3 inflammasome / positive regulation of monocyte chemotaxis / positive regulation of T cell migration / response to yeast / apolipoprotein binding / frizzled binding / acetylcholine receptor binding / nuclear envelope lumen / smooth endoplasmic reticulum / positive regulation of protein kinase A signaling / associative learning / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models|
Function and homology information
|Source||Homo sapiens / human /|
|Authors||Krotee P / Griner SL / Sawaya MR / Cascio D / Rodriguez JA / Shi D / Philipp S / Murray K / Saelices L / Lee J / Seidler P / Glabe CG / Jiang L / Gonen T / Eisenberg DS|
|Citation||Journal: J. Biol. Chem. / Year: 2018|
Title: Common fibrillar spines of amyloid-β and human islet amyloid polypeptide revealed by microelectron diffraction and structure-based inhibitors.
Authors: Pascal Krotee / Sarah L Griner / Michael R Sawaya / Duilio Cascio / Jose A Rodriguez / Dan Shi / Stephan Philipp / Kevin Murray / Lorena Saelices / Ji Lee / Paul Seidler / Charles G Glabe / Lin Jiang / Tamir Gonen / David S Eisenberg
Abstract: Amyloid-β (Aβ) and human islet amyloid polypeptide (hIAPP) aggregate to form amyloid fibrils that deposit in tissues and are associated with Alzheimer's disease (AD) and type II diabetes (T2D), ...Amyloid-β (Aβ) and human islet amyloid polypeptide (hIAPP) aggregate to form amyloid fibrils that deposit in tissues and are associated with Alzheimer's disease (AD) and type II diabetes (T2D), respectively. Individuals with T2D have an increased risk of developing AD, and conversely, AD patients have an increased risk of developing T2D. Evidence suggests that this link between AD and T2D might originate from a structural similarity between aggregates of Aβ and hIAPP. Using the cryoEM method microelectron diffraction, we determined the atomic structures of 11-residue segments from both Aβ and hIAPP, termed Aβ(24-34) WT and hIAPP(19-29) S20G, with 64% sequence similarity. We observed a high degree of structural similarity between their backbone atoms (0.96-Å root mean square deviation). Moreover, fibrils of these segments induced amyloid formation through self- and cross-seeding. Furthermore, inhibitors designed for one segment showed cross-efficacy for full-length Aβ and hIAPP and reduced cytotoxicity of both proteins, although by apparently blocking different cytotoxic mechanisms. The similarity of the atomic structures of Aβ(24-34) WT and hIAPP(19-29) S20G offers a molecular model for cross-seeding between Aβ and hIAPP.
Copyright: 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
|Validation Report||PDB-ID: 5vos|
SummaryFull reportAbout validation report
|Date||Deposition: May 3, 2017 / Header (metadata) release: Jul 19, 2017 / Map release: Jan 3, 2018 / Last update: Mar 7, 2018|
Downloads & links
|File||emd_8720.map.gz (map file in CCP4 format, 217 KB)|
|Projections & slices|
Images are generated by Spider package.
(generated in cubic-lattice coordinate)
|Voxel size||X: 0.4675 Å / Y: 0.3916 Å / Z: 0.4648 Å|
CCP4 map header:
-Entire Fibrils of Amyloid Beta segment 24-34
|Entire||Name: Fibrils of Amyloid Beta segment 24-34 / Number of components: 3|
-Component #1: protein, Fibrils of Amyloid Beta segment 24-34
|Protein||Name: Fibrils of Amyloid Beta segment 24-34 / Recombinant expression: No|
|Source||Species: Homo sapiens / human /|
-Component #2: protein, Amyloid beta A4 protein
|Protein||Name: Amyloid beta A4 protein / Recombinant expression: No|
|Mass||Theoretical: 1.029213 kDa|
-Component #3: ligand, water
|Ligand||Name: water / Number of Copies: 1 / Recombinant expression: No|
|Mass||Theoretical: 1.801505 MDa|
|Specimen state||3D array|
|Crystal parameters||Space group: P 21 / A: 18.78 Å / B: 4.73 Å / C: 33.47 Å / Alpha: 90 deg. / Beta: 100.017 deg. / Gamma: 90 deg.|
|Crystal grow details||shaking|
|Sample solution||Specimen conc.: 7.5 mg/ml / pH: 4|
|Vitrification||Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE|
-Electron microscopy imaging
Model: Tecnai F20 / Image courtesy: FEI Company
|Imaging||Microscope: FEI TECNAI F20|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Electron dose: 0.03 e/Å2 / Illumination mode: FLOOD BEAM|
|Lens||Imaging mode: DIFFRACTION|
|Specimen Holder||Model: GATAN LIQUID NITROGEN|
|Camera||Detector: TVIPS TEMCAM-F416 (4k x 4k)|
|Processing||Method: electron crystallography|
|3D reconstruction||Resolution method: DIFFRACTION PATTERN/LAYERLINES|
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