+
Open data
-
Basic information
Entry | Database: PDB / ID: 6y1a | ||||||
---|---|---|---|---|---|---|---|
Title | Amyloid fibril structure of islet amyloid polypeptide | ||||||
![]() | Islet amyloid polypeptide | ||||||
![]() | HORMONE / amylin / iapp / amyloid fibril / diabetes | ||||||
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: 4.2 Å | ||||||
![]() | Roeder, C. / Kupreichyk, T. / Gremer, L. / Schaefer, L.U. / Pothula, K.R. / Ravelli, R.B.G. / Willbold, D. / Hoyer, W. / Schroder, G.F. | ||||||
Funding support | European Union, 1items
| ||||||
![]() | ![]() Title: Cryo-EM structure of islet amyloid polypeptide fibrils reveals similarities with amyloid-β fibrils. Authors: Christine Röder / Tatsiana Kupreichyk / Lothar Gremer / Luisa U Schäfer / Karunakar R Pothula / Raimond B G Ravelli / Dieter Willbold / Wolfgang Hoyer / Gunnar F Schröder / ![]() ![]() Abstract: Amyloid deposits consisting of fibrillar islet amyloid polypeptide (IAPP) in pancreatic islets are associated with beta-cell loss and have been implicated in type 2 diabetes (T2D). Here, we applied ...Amyloid deposits consisting of fibrillar islet amyloid polypeptide (IAPP) in pancreatic islets are associated with beta-cell loss and have been implicated in type 2 diabetes (T2D). Here, we applied cryo-EM to reconstruct densities of three dominant IAPP fibril polymorphs, formed in vitro from synthetic human IAPP. An atomic model of the main polymorph, built from a density map of 4.2-Å resolution, reveals two S-shaped, intertwined protofilaments. The segment 21-NNFGAIL-27, essential for IAPP amyloidogenicity, forms the protofilament interface together with Tyr37 and the amidated C terminus. The S-fold resembles polymorphs of Alzheimer's disease (AD)-associated amyloid-β (Aβ) fibrils, which might account for the epidemiological link between T2D and AD and reports on IAPP-Aβ cross-seeding in vivo. The results structurally link the early-onset T2D IAPP genetic polymorphism (encoding Ser20Gly) with the AD Arctic mutation (Glu22Gly) of Aβ and support the design of inhibitors and imaging probes for IAPP fibrils. #1: ![]() Title: Amyloid fibril structure of islet amyloid polypeptide by cryo-electron microscopy reveals similarities with amyloid beta Authors: Roeder, C. / Kupreichyk, T. / Gremer, L. / Schaefer, L.U. / Pothula, K.R. / Ravelli, R.B.G. / Willbold, D. / Hoyer, W. / Schroder, G.F. | ||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 80.1 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 63 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 10669MC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data | |
EM raw data | ![]() Data #1: MotionCor2-aligned single frame of islet amyloid polypeptide fibrils [micrographs - single frame]) |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein/peptide | Mass: 3909.304 Da / Num. of mol.: 16 / Source method: obtained synthetically / Source: (synth.) ![]() #2: Chemical | ChemComp-NH2 / Has ligand of interest | N | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
-
Sample preparation
Component | Name: Amyloid fibril of the islet amyloid polypeptide (IAPP) Type: COMPLEX / Details: The fibril consists of IAPP monomers. / Entity ID: #1 / Source: NATURAL |
---|---|
Molecular weight | Value: 10.6 kDa/nm / Experimental value: NO |
Source (natural) | Organism: ![]() |
Buffer solution | pH: 6 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TECNAI ARCTICA |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Average exposure time: 46 sec. / Electron dose: 41.4 e/Å2 / Detector mode: COUNTING / Film or detector model: FEI FALCON III (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 1330 |
EM imaging optics | Phase plate: OTHER |
-
Processing
EM software |
| ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: NONE | ||||||||||||||||
Helical symmerty | Angular rotation/subunit: 178.23 ° / Axial rise/subunit: 2.351 Å / Axial symmetry: C1 | ||||||||||||||||
3D reconstruction | Resolution: 4.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 37120 Details: the data set was split by whole fibrils and then refined independently for 25 iterations to yield the two half maps. Num. of class averages: 1 / Symmetry type: HELICAL | ||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL |