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- PDB-6vw2: Cryo-EM structure of human islet amyloid polypeptide (hIAPP, or a... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6vw2 | ||||||
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Title | Cryo-EM structure of human islet amyloid polypeptide (hIAPP, or amylin) fibrils | ||||||
![]() | Islet amyloid polypeptide (SUMO-tagged) | ||||||
![]() | PROTEIN FIBRIL / ![]() ![]() ![]() | ||||||
Function / homology | ![]() SUMO is conjugated to E1 (UBA2:SAE1) / SUMOylation of nuclear envelope proteins / SUMO is transferred from E1 to E2 (UBE2I, UBC9) / : / SUMO is proteolytically processed / SUMOylation of transcription factors / Postmitotic nuclear pore complex (NPC) reformation / SUMOylation of transcription cofactors / SUMOylation of DNA damage response and repair proteins / amylin receptor signaling pathway ...SUMO is conjugated to E1 (UBA2:SAE1) / SUMOylation of nuclear envelope proteins / SUMO is transferred from E1 to E2 (UBE2I, UBC9) / : / SUMO is proteolytically processed / SUMOylation of transcription factors / Postmitotic nuclear pore complex (NPC) reformation / SUMOylation of transcription cofactors / SUMOylation of DNA damage response and repair proteins / amylin receptor signaling pathway / Calcitonin-like ligand receptors / SUMOylation of DNA replication proteins / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ![]() ![]() | ||||||
![]() | Cao, Q. / Boyer, D.R. / Sawaya, M.R. / Eisenberg, D.S. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structure and inhibitor design of human IAPP (amylin) fibrils. Authors: Qin Cao / David R Boyer / Michael R Sawaya / Peng Ge / David S Eisenberg / ![]() Abstract: Human islet amyloid polypeptide (hIAPP) functions as a glucose-regulating hormone but deposits as amyloid fibrils in more than 90% of patients with type II diabetes (T2D). Here we report the cryo-EM ...Human islet amyloid polypeptide (hIAPP) functions as a glucose-regulating hormone but deposits as amyloid fibrils in more than 90% of patients with type II diabetes (T2D). Here we report the cryo-EM structure of recombinant full-length hIAPP fibrils. The fibril is composed of two symmetrically related protofilaments with ordered residues 14-37. Our hIAPP fibril structure (i) supports the previous hypothesis that residues 20-29 constitute the core of the hIAPP amyloid; (ii) suggests a molecular mechanism for the action of the hIAPP hereditary mutation S20G; (iii) explains why the six residue substitutions in rodent IAPP prevent aggregation; and (iv) suggests regions responsible for the observed hIAPP cross-seeding with β-amyloid. Furthermore, we performed structure-based inhibitor design to generate potential hIAPP aggregation inhibitors. Four of the designed peptides delay hIAPP aggregation in vitro, providing a starting point for the development of T2D therapeutics and proof of concept that the capping strategy can be used on full-length cryo-EM fibril structures. | ||||||
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 | ![]() | 67.9 KB | Display | ![]() |
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PDB format | ![]() | 41.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 21410MC M: map data used to model this data C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data size: 1.9 TB Data #1: Unaligned K2 movies of unseeded, recombinant hIAPP amyloid fibrils [micrographs - multiframe]) |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 17274.273 Da / Num. of mol.: 10 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() Strain: ATCC 204508 / S288c / Gene: SMT3, YDR510W, D9719.15, IAPP / Production host: ![]() ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
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Sample preparation
Component | Name: hIAPP fibril / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Vitrification![]() | Cryogen name: ETHANE |
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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![]() ![]() |
Image recording | Average exposure time: 8 sec. / Electron dose: 44 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: 179.42 ° / Axial rise/subunit: 2.406 Å / Axial symmetry: C1 | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 25767 / Symmetry type: HELICAL |