+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-0021 | |||||||||
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Title | Single protofilament beta-2-microglobulin amyloid fibril | |||||||||
Map data | Single protofilament beta-2-microglobulin amyloid fibril | |||||||||
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 / negative regulation of receptor binding / DAP12 interactions / 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 / negative regulation of receptor binding / DAP12 interactions / 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 / peptide antigen assembly with MHC class I protein complex / ER to Golgi transport vesicle membrane / 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 / negative regulation of neurogenesis / positive regulation of receptor-mediated endocytosis / peptide antigen assembly with MHC class II protein complex / multicellular organismal-level iron ion homeostasis / 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 / antigen processing and presentation of exogenous peptide antigen via MHC class II / negative regulation of epithelial cell proliferation / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / positive regulation of immune response / Interferon gamma signaling / positive regulation of T cell activation / Modulation by Mtb of host immune system / sensory perception of smell / negative regulation of neuron projection development / positive regulation of protein binding / tertiary granule lumen / DAP12 signaling / 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 / external side of plasma membrane / lysosomal 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: 6.69 Å | |||||||||
Authors | Iadanza MG / Ranson NA | |||||||||
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
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
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Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_0021.map.gz | 10.6 MB | EMDB map data format | |
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Header (meta data) | emd-0021-v30.xml emd-0021.xml | 12.9 KB 12.9 KB | Display Display | EMDB header |
Images | emd_0021.png | 45.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-0021 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0021 | HTTPS FTP |
-Validation report
Summary document | emd_0021_validation.pdf.gz | 196.1 KB | Display | EMDB validaton report |
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Full document | emd_0021_full_validation.pdf.gz | 195.2 KB | Display | |
Data in XML | emd_0021_validation.xml.gz | 6.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0021 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0021 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_0021.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Single protofilament beta-2-microglobulin amyloid fibril | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : Single protofilament beta-2-microglobulin amyloid fibril
Entire | Name: Single protofilament beta-2-microglobulin amyloid fibril |
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Components |
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-Supramolecule #1: Single protofilament beta-2-microglobulin amyloid fibril
Supramolecule | Name: Single 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: 11.7 KDa |
-Macromolecule #1: Human beta-2-microglobulin
Macromolecule | Name: Human beta-2-microglobulin / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: IQRTPKIQVY SRHPAENGKS NFLNCYVSGF HPSDIEVDLL KNGERIEKVE HSDLSFSKDW SFYLLYYTE FTPTEKDEYA CRVNHVTLSQ PKIVKWDRDM |
-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: 0.00325 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
Final reconstruction | Number classes used: 1 Applied symmetry - Helical parameters - Δz: 4.9 Å Applied symmetry - Helical parameters - Δ&Phi: -0.639 ° Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric) Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 6.69 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: RELION / Details: Resolution estimated using rmeasure software / Number images used: 7012 |
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CTF correction | Software: (Name: RELION (ver. 2.1), Gctf) |
Startup model | Type of model: OTHER Details: Double protofilament map from same study Filtered to 60 Angstrom resolution |
Final angle assignment | Type: NOT APPLICABLE / Software - Name: RELION (ver. 2.1) |