+Open data
-Basic information
Entry | Database: PDB / ID: 6zrf | |||||||||
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Title | amyloid structure of amylin (IAPP - islet amyloid polypeptide) | |||||||||
Components | Islet amyloid polypeptide | |||||||||
Keywords | PROTEIN FIBRIL / amyloid fibril type-2-diabetes hormone | |||||||||
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 / bone resorption ...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 | synthetic construct (others) | |||||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
Authors | Gallardo, R.U. / Iadanza, M.G. / Ranson, N.A. / Radford, S.E. | |||||||||
Funding support | United Kingdom, 2items
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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 | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6zrf.cif.gz | 55.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6zrf.ent.gz | 44.6 KB | Display | PDB format |
PDBx/mmJSON format | 6zrf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6zrf_validation.pdf.gz | 926.3 KB | Display | wwPDB validaton report |
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Full document | 6zrf_full_validation.pdf.gz | 941.6 KB | Display | |
Data in XML | 6zrf_validation.xml.gz | 20.5 KB | Display | |
Data in CIF | 6zrf_validation.cif.gz | 28.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/zr/6zrf ftp://data.pdbj.org/pub/pdb/validation_reports/zr/6zrf | HTTPS FTP |
-Related structure data
Related structure data | 11380MC 6zrqC 6zrrC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein/peptide | Mass: 3908.319 Da / Num. of mol.: 12 / Source method: obtained synthetically / Details: TYC = C-terminal amidated Tyr / Source: (synth.) synthetic construct (others) / References: UniProt: P10997 Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: HELICAL ARRAY / 3D reconstruction method: helical reconstruction |
-Sample preparation
Component | Name: amyloid fibril of amylin (islet amyloid polipeptide) / Type: COMPLEX Details: produced synthetically, oxidised, C-terminally amidated, fibrillated in vitro Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 1.625 kDa/nm / Experimental value: NO |
Source (natural) | Organism: synthetic construct (others) |
Buffer solution | pH: 6.8 |
Buffer component | Conc.: 20 mM / Name: Ammonium acetate / Formula: NH4CH3CO2 |
Specimen | Conc.: 0.18 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Homemade |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 277 K |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 14 sec. / Electron dose: 50.07 e/Å2 / Detector mode: INTEGRATING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
EM imaging optics | Energyfilter name: GIF Quantum LS / Energyfilter slit width: 20 eV |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: 178.23 ° / Axial rise/subunit: 2.43 Å / Axial symmetry: C1 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 32846 / Symmetry type: HELICAL |