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Yorodumi- EMDB-11383: three-protofilament amyloid structure of S20G variant of human am... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-11383 | |||||||||
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Title | three-protofilament amyloid structure of S20G variant of human amylin (IAPP - Islet Amyloid Polypeptide) | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information : / amylin receptor signaling pathway / Calcitonin-like ligand receptors / negative regulation of amyloid fibril formation / negative regulation of bone resorption / eating behavior / negative regulation of osteoclast differentiation / positive regulation of protein kinase A signaling / Regulation of gene expression in beta cells / negative regulation of protein-containing complex assembly ...: / amylin receptor signaling pathway / Calcitonin-like ligand receptors / negative regulation of amyloid fibril formation / negative regulation of bone resorption / eating behavior / negative regulation of osteoclast differentiation / positive regulation of protein kinase A signaling / Regulation of gene expression in beta cells / negative regulation of protein-containing complex assembly / positive regulation of calcium-mediated signaling / bone resorption / sensory perception of pain / osteoclast differentiation / hormone activity / cell-cell signaling / amyloid-beta binding / G alpha (s) signalling events / positive regulation of MAPK cascade / receptor ligand activity / positive regulation of apoptotic process / Amyloid fiber formation / signaling receptor binding / lipid binding / apoptotic process / signal transduction / extracellular space / extracellular region / identical protein binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 4.0 Å | |||||||||
Authors | Gallardo RU / Iadanza MG / Ranson NA / Radford SE | |||||||||
Funding support | United Kingdom, 2 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2020 Title: Fibril structures of diabetes-related amylin variants reveal a basis for surface-templated assembly. Authors: Rodrigo Gallardo / Matthew G Iadanza / Yong Xu / George R Heath / Richard Foster / Sheena E Radford / Neil A Ranson / Abstract: Aggregation of the peptide hormone amylin into amyloid deposits is a pathological hallmark of type-2 diabetes (T2D). While no causal link between T2D and amyloid has been established, the S20G ...Aggregation of the peptide hormone amylin into amyloid deposits is a pathological hallmark of type-2 diabetes (T2D). While no causal link between T2D and amyloid has been established, the S20G mutation in amylin is associated with early-onset T2D. Here we report cryo-EM structures of amyloid fibrils of wild-type human amylin and its S20G variant. The wild-type fibril structure, solved to 3.6-Å resolution, contains two protofilaments, each built from S-shaped subunits. S20G fibrils, by contrast, contain two major polymorphs. Their structures, solved at 3.9-Å and 4.0-Å resolution, respectively, share a common two-protofilament core that is distinct from the wild-type structure. Remarkably, one polymorph contains a third subunit with another, distinct, cross-β conformation. The presence of two different backbone conformations within the same fibril may explain the increased aggregation propensity of S20G, and illustrates a potential structural basis for surface-templated fibril assembly. | |||||||||
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_11383.map.gz | 4.6 MB | EMDB map data format | |
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Header (meta data) | emd-11383-v30.xml emd-11383.xml | 19.9 KB 19.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_11383_fsc.xml | 10.7 KB | Display | FSC data file |
Images | emd_11383.png | 38.6 KB | ||
Masks | emd_11383_msk_1.map | 103 MB | Mask map | |
Others | emd_11383_additional_1.map.gz emd_11383_half_map_1.map.gz emd_11383_half_map_2.map.gz | 80.8 MB 80.6 MB 80.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-11383 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-11383 | HTTPS FTP |
-Validation report
Summary document | emd_11383_validation.pdf.gz | 389.3 KB | Display | EMDB validaton report |
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Full document | emd_11383_full_validation.pdf.gz | 388.5 KB | Display | |
Data in XML | emd_11383_validation.xml.gz | 16.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11383 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11383 | HTTPS FTP |
-Related structure data
Related structure data | 6zrrMC 6zrfC 6zrqC C: citing same article (ref.) M: atomic model generated by this map |
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Similar 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_11383.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.065 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_11383_msk_1.map | ||||||||||||
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Density Histograms |
-Additional map: 3D-autorefine map
File | emd_11383_additional_1.map | ||||||||||||
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Annotation | 3D-autorefine map | ||||||||||||
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Density Histograms |
-Half map: 3D-autorefine half2 map
File | emd_11383_half_map_1.map | ||||||||||||
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Annotation | 3D-autorefine half2 map | ||||||||||||
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Density Histograms |
-Half map: 3D-autorefine half1 map
File | emd_11383_half_map_2.map | ||||||||||||
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Annotation | 3D-autorefine half1 map | ||||||||||||
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Density Histograms |
-Sample components
-Entire : three-protofilament amyloid fibril of S20G variant of amylin
Entire | Name: three-protofilament amyloid fibril of S20G variant of amylin |
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Components |
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-Supramolecule #1: three-protofilament amyloid fibril of S20G variant of amylin
Supramolecule | Name: three-protofilament amyloid fibril of S20G variant of amylin type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: three-protofilament amyloid fibril of S20G variant of amylin
Supramolecule | Name: three-protofilament amyloid fibril of S20G variant of amylin type: complex / ID: 2 / Parent: 1 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: synthetic construct (others) |
-Macromolecule #1: Islet amyloid polypeptide
Macromolecule | Name: Islet amyloid polypeptide / type: protein_or_peptide / ID: 1 / Details: TYC = C-terminally amidated Tyr / Number of copies: 18 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 3.878293 KDa |
Sequence | String: KCNTATCATQ RLANFLVHSG NNFGAILSST NVGSNT(TYC) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Concentration | 0.12 mg/mL |
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Buffer | pH: 6.8 / Component - Concentration: 20.0 mM / Component - Formula: NH4CH3CO / Component - Name: ammonium acetate |
Grid | Model: Homemade / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 85 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
Details | Synthetically produced, oxidised and C-terminally amidated |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Quantum LS / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average exposure time: 13.0 sec. / Average electron dose: 54.73 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 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 |