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Yorodumi- PDB-7m65: Cryo-EM structure of human islet amyloid polypeptide (hIAPP, or a... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7m65 | ||||||
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Title | Cryo-EM structure of human islet amyloid polypeptide (hIAPP, or amylin) fibrils seeded by patient extracted fibrils, polymorph 4 | ||||||
Components | Islet amyloid polypeptide | ||||||
Keywords | PROTEIN FIBRIL / hIAPP / type II diabetes / amyloid | ||||||
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 | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 4.1 Å | ||||||
Authors | Cao, Q. / Boyer, D.R. / Sawaya, M.R. / Eisenberg, D.S. | ||||||
Funding support | United States, 1items
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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 | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7m65.cif.gz | 50.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7m65.ent.gz | 40.1 KB | Display | PDB format |
PDBx/mmJSON format | 7m65.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7m65_validation.pdf.gz | 799.2 KB | Display | wwPDB validaton report |
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Full document | 7m65_full_validation.pdf.gz | 808.7 KB | Display | |
Data in XML | 7m65_validation.xml.gz | 18.9 KB | Display | |
Data in CIF | 7m65_validation.cif.gz | 27.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/m6/7m65 ftp://data.pdbj.org/pub/pdb/validation_reports/m6/7m65 | HTTPS FTP |
-Related structure data
Related structure data | 23689MC 7m61C 7m62C 7m64C M: map data used to model this data C: citing same article (ref.) |
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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
-Assembly
Deposited unit |
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1 |
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Symmetry | Helical symmetry: (Circular symmetry: 1 / Dyad axis: no / N subunits divisor: 1 / Num. of operations: 5 / Rise per n subunits: 4.81 Å / Rotation per n subunits: -2.94 °) |
-Components
#1: Protein/peptide | Mass: 3907.312 Da / Num. of mol.: 10 / Fragment: C-terminal amidated peptide (UNP residues 34-70) / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P10997 |
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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 |
-Sample preparation
Component | Name: hIAPP fibril / Type: COMPLEX Details: Synthetic hIAPP seeded by hIAPP fibrils extracted from a patient with Type II Diabetes Entity ID: all / Source: NATURAL |
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Molecular weight | Units: KILODALTONS/NANOMETER / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 298 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 |
Image recording | Electron dose: 45 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 3 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: -2.94 ° / Axial rise/subunit: 4.81 Å / Axial symmetry: C1 | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 20365 / Symmetry type: HELICAL | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | B value: 100 / Protocol: AB INITIO MODEL / Space: REAL |