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- PDB-6zrq: two-protofilament amyloid structure of S20G variant of human amyl... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6zrq | |||||||||
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Title | two-protofilament amyloid structure of S20G variant of human amylin (IAPP - islet amyloid polypeptide) | |||||||||
![]() | Islet amyloid polypeptide | |||||||||
![]() | PROTEIN FIBRIL / amyloid fibril type-2-diabetes early-onset | |||||||||
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 | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
![]() | Gallardo, R.U. / Iadanza, M.G. / Ranson, N.A. / Radford, S.E. | |||||||||
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 | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 86.8 KB | Display | ![]() |
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PDB format | ![]() | 74.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 11382MC ![]() 6zrfC ![]() 6zrrC C: citing same article ( M: map data used to model this data |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein/peptide | Mass: 3878.293 Da / Num. of mol.: 12 / Mutation: S20G / Source method: obtained synthetically / Details: TYC = C-terminal amidated Tyr / Source: (synth.) ![]() Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
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Sample preparation
Component |
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Molecular weight | Experimental value: NO | ||||||||||||||||||
Source (natural) | Organism: ![]() | ||||||||||||||||||
Source (recombinant) | Organism: synthetic construct (others) | ||||||||||||||||||
Buffer solution | pH: 6.8 | ||||||||||||||||||
Buffer component | Conc.: 20 mM / Name: ammonium acetate / Formula: NH4CH3CO | ||||||||||||||||||
Specimen | Conc.: 0.12 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Synthetically produced, oxidised and C-terminally amidated | ||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Homemade | ||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 85 % / Chamber temperature: 277 K |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 130000 X / Cs: 2.7 mm / C2 aperture diameter: 100 µm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 13 sec. / Electron dose: 54.73 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
EM imaging optics | Energyfilter name: GIF Quantum LS / Energyfilter slit width: 20 eV |
Image scans | Movie frames/image: 52 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: 179.05 ° / Axial rise/subunit: 2.41 Å / Axial symmetry: C1 | ||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 64274 | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 11901 / Num. of class averages: 1 / Symmetry type: HELICAL |