+Open data
-Basic information
Entry | Database: PDB / ID: 6mst | |||||||||
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Title | Cryo-EM structure of human AA amyloid fibril | |||||||||
Components | Serum amyloid A-1 protein | |||||||||
Keywords | PROTEIN FIBRIL / AA-amyloidosis / Serum Amyloid A / cross-beta / helical | |||||||||
Function / homology | Function and homology information Scavenging by Class B Receptors / lymphocyte chemotaxis / positive regulation of interleukin-1 production / high-density lipoprotein particle / Formyl peptide receptors bind formyl peptides and many other ligands / macrophage chemotaxis / regulation of protein secretion / cytoplasmic microtubule / TRAF6 mediated NF-kB activation / Advanced glycosylation endproduct receptor signaling ...Scavenging by Class B Receptors / lymphocyte chemotaxis / positive regulation of interleukin-1 production / high-density lipoprotein particle / Formyl peptide receptors bind formyl peptides and many other ligands / macrophage chemotaxis / regulation of protein secretion / cytoplasmic microtubule / TRAF6 mediated NF-kB activation / Advanced glycosylation endproduct receptor signaling / endocytic vesicle lumen / neutrophil chemotaxis / positive regulation of cell adhesion / acute-phase response / positive regulation of cytokine production / G protein-coupled receptor binding / TAK1-dependent IKK and NF-kappa-B activation / platelet activation / negative regulation of inflammatory response / heparin binding / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / G alpha (q) signalling events / Interleukin-4 and Interleukin-13 signaling / Amyloid fiber formation / extracellular exosome / extracellular region Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 2.7 Å | |||||||||
Authors | Loerch, S. / Rennegarbe, M. / Liberta, F. / Grigorieff, N. / Fandrich, M. / Schmidt, M. | |||||||||
Funding support | Germany, 2items
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Citation | Journal: Nat Commun / Year: 2019 Title: Cryo-EM fibril structures from systemic AA amyloidosis reveal the species complementarity of pathological amyloids. Authors: Falk Liberta / Sarah Loerch / Matthies Rennegarbe / Angelika Schierhorn / Per Westermark / Gunilla T Westermark / Bouke P C Hazenberg / Nikolaus Grigorieff / Marcus Fändrich / Matthias Schmidt / Abstract: Systemic AA amyloidosis is a worldwide occurring protein misfolding disease of humans and animals. It arises from the formation of amyloid fibrils from the acute phase protein serum amyloid A. Here, ...Systemic AA amyloidosis is a worldwide occurring protein misfolding disease of humans and animals. It arises from the formation of amyloid fibrils from the acute phase protein serum amyloid A. Here, we report the purification and electron cryo-microscopy analysis of amyloid fibrils from a mouse and a human patient with systemic AA amyloidosis. The obtained resolutions are 3.0 Å and 2.7 Å for the murine and human fibril, respectively. The two fibrils differ in fundamental properties, such as presence of right-hand or left-hand twisted cross-β sheets and overall fold of the fibril proteins. Yet, both proteins adopt highly similar β-arch conformations within the N-terminal ~21 residues. Our data demonstrate the importance of the fibril protein N-terminus for the stability of the analyzed amyloid fibril morphologies and suggest strategies of combating this disease by interfering with specific fibril polymorphs. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6mst.cif.gz | 118.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6mst.ent.gz | 94.7 KB | Display | PDB format |
PDBx/mmJSON format | 6mst.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6mst_validation.pdf.gz | 950.3 KB | Display | wwPDB validaton report |
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Full document | 6mst_full_validation.pdf.gz | 950.5 KB | Display | |
Data in XML | 6mst_validation.xml.gz | 28.5 KB | Display | |
Data in CIF | 6mst_validation.cif.gz | 42.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ms/6mst ftp://data.pdbj.org/pub/pdb/validation_reports/ms/6mst | HTTPS FTP |
-Related structure data
Related structure data | 9232MC 8910C 6dsoC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10734 (Title: Cryo electron microscopy of ex-vivo human SAA amyloid fibrils Data size: 1.1 TB Data #1: Unaligned multiframe micrographs of ex-vivo human SAA1 [micrographs - multiframe]) |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 7481.154 Da / Num. of mol.: 12 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P0DJI8 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: HELICAL ARRAY / 3D reconstruction method: helical reconstruction |
-Sample preparation
Component | Name: human AA amyloid fibril / Type: COMPLEX / Entity ID: all / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) / Organ: kidney |
Buffer solution | pH: 7 |
Buffer component | Formula: ddH2O |
Specimen | Conc.: 0.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: 15 mA / Grid material: COPPER / Grid type: C-flat-1.2/1.3 4C |
Vitrification | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 293 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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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 magnification: 130000 X / Nominal defocus max: -2500 nm / Nominal defocus min: -500 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Average exposure time: 12 sec. / Electron dose: 40 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
Image scans | Movie frames/image: 40 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: 0.79 ° / Axial rise/subunit: 2.4 Å / Axial symmetry: C1 | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 93025 | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 91872 / Symmetry type: HELICAL | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL |