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Yorodumi- EMDB-23687: Cryo-EM structure of human islet amyloid polypeptide (hIAPP, or a... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23687 | |||||||||
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Title | Cryo-EM structure of human islet amyloid polypeptide (hIAPP, or amylin) fibrils seeded by patient extracted fibrils, polymorph 2 | |||||||||
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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 / positive regulation of protein kinase A signaling / negative regulation of osteoclast differentiation / 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 / positive regulation of protein kinase A signaling / negative regulation of osteoclast differentiation / 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 | Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Cao Q / Boyer DR / Sawaya MR / Eisenberg DS | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2021 Title: Cryo-EM structures of hIAPP fibrils seeded by patient-extracted fibrils reveal new polymorphs and conserved fibril cores. Authors: Qin Cao / David R Boyer / Michael R Sawaya / Romany Abskharon / Lorena Saelices / Binh A Nguyen / Jiahui Lu / Kevin A Murray / Fouad Kandeel / David S Eisenberg / Abstract: Amyloidosis of human islet amyloid polypeptide (hIAPP) is a pathological hallmark of type II diabetes (T2D), an epidemic afflicting nearly 10% of the world's population. To visualize disease-relevant ...Amyloidosis of human islet amyloid polypeptide (hIAPP) is a pathological hallmark of type II diabetes (T2D), an epidemic afflicting nearly 10% of the world's population. To visualize disease-relevant hIAPP fibrils, we extracted amyloid fibrils from islet cells of a T2D donor and amplified their quantity by seeding synthetic hIAPP. Cryo-EM studies revealed four fibril polymorphic atomic structures. Their resemblance to four unseeded hIAPP fibrils varies from nearly identical (TW3) to non-existent (TW2). The diverse repertoire of hIAPP polymorphs appears to arise from three distinct protofilament cores entwined in different combinations. The structural distinctiveness of TW1, TW2 and TW4 suggests they may be faithful replications of the pathogenic seeds. If so, the structures determined here provide the most direct view yet of hIAPP amyloid fibrils formed during T2D. | |||||||||
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_23687.map.gz | 7.1 MB | EMDB map data format | |
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Header (meta data) | emd-23687-v30.xml emd-23687.xml | 11.3 KB 11.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_23687_fsc.xml | 9.1 KB | Display | FSC data file |
Images | emd_23687.png | 161.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23687 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23687 | HTTPS FTP |
-Validation report
Summary document | emd_23687_validation.pdf.gz | 464.8 KB | Display | EMDB validaton report |
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Full document | emd_23687_full_validation.pdf.gz | 464.4 KB | Display | |
Data in XML | emd_23687_validation.xml.gz | 10.3 KB | Display | |
Data in CIF | emd_23687_validation.cif.gz | 13.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23687 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23687 | HTTPS FTP |
-Related structure data
Related structure data | 7m62MC 7m61C 7m64C 7m65C C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | |
EM raw data | EMPIAR-10868 (Title: Cryo electron microscopy of hIAPP fibrils seeded by patient-extracted fibrils Data size: 9.9 TB Data #1: Unaligned K3 movies of hIAPP fibrils seeded by disease fibrils [micrographs - multiframe]) |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_23687.map.gz / Format: CCP4 / Size: 8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.055 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : hIAPP fibril
Entire | Name: hIAPP fibril |
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Components |
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-Supramolecule #1: hIAPP fibril
Supramolecule | Name: hIAPP fibril / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all Details: Synthetic hIAPP seeded by hIAPP fibrils extracted from a patient with Type II Diabetes |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Islet amyloid polypeptide
Macromolecule | Name: Islet amyloid polypeptide / type: protein_or_peptide / ID: 1 / Number of copies: 10 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 3.907312 KDa |
Sequence | String: KCNTATCATQ RLANFLVHSS NNFGAILSST NVGSNTY(NH2) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.4 / Details: PBS buffer |
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Detector mode: SUPER-RESOLUTION / Number grids imaged: 3 / Average electron dose: 45.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL / Overall B value: 98 |
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Output model | PDB-7m62: |