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- EMDB-11382: two-protofilament amyloid structure of S20G variant of human amyl... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-11382 | |||||||||
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Title | two-protofilament amyloid structure of S20G variant of human amylin (IAPP - islet amyloid polypeptide) | |||||||||
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Function / homology | ![]() : / 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 / bone resorption / sensory perception of pain / positive regulation of calcium-mediated signaling / 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 | ![]() | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
![]() | Gallardo RU / Iadanza MG / Ranson NA / Radford SE | |||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 4.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13.2 KB 13.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.7 KB | Display | ![]() |
Images | ![]() | 26.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6zrqMC ![]() 6zrfC ![]() 6zrrC C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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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
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Sample components
-Entire : two-protofilament amyloid fibrils of S20G variant of amylin
Entire | Name: two-protofilament amyloid fibrils of S20G variant of amylin |
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Components |
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-Supramolecule #1: two-protofilament amyloid fibrils of S20G variant of amylin
Supramolecule | Name: two-protofilament amyloid fibrils of S20G variant of amylin type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: two-protofilament amyloid fibrils of S20G variant of amylin
Supramolecule | Name: two-protofilament amyloid fibrils of S20G variant of amylin type: complex / ID: 2 / Parent: 1 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
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-terminal amidated Tyr / Number of copies: 12 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 3.878293 KDa |
Sequence | String: KCNTATCATQ RLANFLVHSG NNFGAILSST NVGSNT(TYC) |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | helical reconstruction |
Aggregation state | filament |
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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 |
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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: ![]() |
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 |