+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-0014 | ||||||||||||||||||
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Title | Two protofilament beta-2-microglobulin amyloid fibril | ||||||||||||||||||
Map data | Beta-2-microglobulin amyloid fibril - two protofilamets | ||||||||||||||||||
Sample |
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Function / homology | Function and homology information positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / positive regulation of receptor binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / negative regulation of receptor binding / cellular response to iron ion / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC ...positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / positive regulation of receptor binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / negative regulation of receptor binding / cellular response to iron ion / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / cellular response to iron(III) ion / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / negative regulation of forebrain neuron differentiation / regulation of erythrocyte differentiation / ER to Golgi transport vesicle membrane / peptide antigen assembly with MHC class I protein complex / regulation of iron ion transport / response to molecule of bacterial origin / MHC class I peptide loading complex / HFE-transferrin receptor complex / T cell mediated cytotoxicity / antigen processing and presentation of endogenous peptide antigen via MHC class I / positive regulation of T cell cytokine production / MHC class I protein complex / multicellular organismal-level iron ion homeostasis / negative regulation of neurogenesis / peptide antigen assembly with MHC class II protein complex / positive regulation of receptor-mediated endocytosis / MHC class II protein complex / cellular response to nicotine / positive regulation of T cell mediated cytotoxicity / specific granule lumen / recycling endosome membrane / phagocytic vesicle membrane / positive regulation of cellular senescence / peptide antigen binding / negative regulation of epithelial cell proliferation / antigen processing and presentation of exogenous peptide antigen via MHC class II / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / Interferon gamma signaling / positive regulation of immune response / Modulation by Mtb of host immune system / sensory perception of smell / positive regulation of T cell activation / positive regulation of protein binding / tertiary granule lumen / DAP12 signaling / negative regulation of neuron projection development / MHC class II protein complex binding / late endosome membrane / iron ion transport / ER-Phagosome pathway / early endosome membrane / T cell differentiation in thymus / protein refolding / protein homotetramerization / intracellular iron ion homeostasis / amyloid fibril formation / learning or memory / Amyloid fiber formation / endoplasmic reticulum lumen / Golgi membrane / lysosomal membrane / external side of plasma membrane / focal adhesion / Neutrophil degranulation / SARS-CoV-2 activates/modulates innate and adaptive immune responses / structural molecule activity / Golgi apparatus / endoplasmic reticulum / protein homodimerization activity / extracellular space / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane / cytosol Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.975 Å | ||||||||||||||||||
Authors | Iadanza MG / Ranson NA | ||||||||||||||||||
Funding support | United Kingdom, United States, 5 items
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Citation | Journal: Nat Commun / Year: 2018 Title: The structure of a β-microglobulin fibril suggests a molecular basis for its amyloid polymorphism. Authors: Matthew G Iadanza / Robert Silvers / Joshua Boardman / Hugh I Smith / Theodoros K Karamanos / Galia T Debelouchina / Yongchao Su / Robert G Griffin / Neil A Ranson / Sheena E Radford / Abstract: All amyloid fibrils contain a cross-β fold. How this structure differs in fibrils formed from proteins associated with different diseases remains unclear. Here, we combine cryo-EM and MAS-NMR to ...All amyloid fibrils contain a cross-β fold. How this structure differs in fibrils formed from proteins associated with different diseases remains unclear. Here, we combine cryo-EM and MAS-NMR to determine the structure of an amyloid fibril formed in vitro from β-microglobulin (βm), the culprit protein of dialysis-related amyloidosis. The fibril is composed of two identical protofilaments assembled from subunits that do not share βm's native tertiary fold, but are formed from similar β-strands. The fibrils share motifs with other amyloid fibrils, but also contain unique features including π-stacking interactions perpendicular to the fibril axis and an intramolecular disulfide that stabilises the subunit fold. We also describe a structural model for a second fibril morphology and show that it is built from the same subunit fold. The results provide insights into the mechanisms of fibril formation and the commonalities and differences within the amyloid fold in different protein sequences. | ||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_0014.map.gz | 5.3 MB | EMDB map data format | |
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Header (meta data) | emd-0014-v30.xml emd-0014.xml | 15.3 KB 15.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_0014_fsc.xml | 10.7 KB | Display | FSC data file |
Images | emd_0014.png | 163.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-0014 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0014 | HTTPS FTP |
-Validation report
Summary document | emd_0014_validation.pdf.gz | 326.9 KB | Display | EMDB validaton report |
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Full document | emd_0014_full_validation.pdf.gz | 326.5 KB | Display | |
Data in XML | emd_0014_validation.xml.gz | 11.9 KB | Display | |
Data in CIF | emd_0014_validation.cif.gz | 15.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0014 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0014 | HTTPS FTP |
-Related structure data
Related structure data | 6gk3MC 0021C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10207 (Title: Beta-2-microglobulin fibrils with multiple polymorphs formed at pH 2 Data size: 294.3 Data #1: Aligned, dose-weighted micrographs [micrographs - single frame]) |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_0014.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Beta-2-microglobulin amyloid fibril - two protofilamets | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : two protofilament beta-2-microglobulin amyloid fibril
Entire | Name: two protofilament beta-2-microglobulin amyloid fibril |
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Components |
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-Supramolecule #1: two protofilament beta-2-microglobulin amyloid fibril
Supramolecule | Name: two protofilament beta-2-microglobulin amyloid fibril / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Molecular weight | Theoretical: 53.3 kDa/nm |
-Macromolecule #1: Beta-2-microglobulin
Macromolecule | Name: Beta-2-microglobulin / type: protein_or_peptide / ID: 1 / Number of copies: 8 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 7.635446 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: FLNCYVSGFH PSDIEVDLLK NGERIEKVEH SDLSFSKDWS FYLLYYTEFT PTEKDEYACR VNHV |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Concentration | 0.025 mg/mL | ||||||||||||
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Buffer | pH: 2.5 Component:
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Grid | Model: Quantifoil R3.5/1 / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 80 % / Chamber temperature: 281.15 K / Instrument: FEI VITROBOT MARK II | ||||||||||||
Details | Quiescent growth at 0.25 mg/ml for 5 weeks, diluted 10x with buffer |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Frames/image: 3-40 / Number grids imaged: 1 / Number real images: 5549 / Average exposure time: 10.0 sec. / Average electron dose: 38.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 0.0032500000000000003 µm / Nominal defocus min: 0.00175 µm / Nominal magnification: 130000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: OTHER |
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Output model | PDB-6gk3: |