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Yorodumi- EMDB-26304: Cryo-EM structure of the pancreatic ATP-sensitive potassium chann... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26304 | |||||||||
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Title | Cryo-EM structure of the pancreatic ATP-sensitive potassium channel bound to ATP and repaglinide with SUR1-out conformation | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information Regulation of insulin secretion / ATP sensitive Potassium channels / ABC-family proteins mediated transport / response to resveratrol / ATP-activated inward rectifier potassium channel activity / inward rectifying potassium channel / cell body fiber / sulfonylurea receptor activity / ventricular cardiac muscle tissue development / CAMKK-AMPK signaling cascade ...Regulation of insulin secretion / ATP sensitive Potassium channels / ABC-family proteins mediated transport / response to resveratrol / ATP-activated inward rectifier potassium channel activity / inward rectifying potassium channel / cell body fiber / sulfonylurea receptor activity / ventricular cardiac muscle tissue development / CAMKK-AMPK signaling cascade / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / ATPase-coupled monoatomic cation transmembrane transporter activity / inward rectifier potassium channel activity / nervous system process / inorganic cation transmembrane transport / regulation of monoatomic ion transmembrane transport / ankyrin binding / Ion homeostasis / response to ATP / response to testosterone / potassium ion import across plasma membrane / action potential / regulation of insulin secretion / voltage-gated potassium channel activity / intercalated disc / potassium channel activity / axolemma / ABC-type transporter activity / negative regulation of insulin secretion / potassium ion transmembrane transport / T-tubule / heat shock protein binding / acrosomal vesicle / regulation of membrane potential / response to ischemia / determination of adult lifespan / positive regulation of protein localization to plasma membrane / cellular response to glucose stimulus / potassium ion transport / sarcolemma / cellular response to nicotine / glucose metabolic process / response to estradiol / cellular response to tumor necrosis factor / nuclear envelope / presynaptic membrane / transmembrane transporter binding / response to hypoxia / endosome / response to xenobiotic stimulus / neuronal cell body / glutamatergic synapse / apoptotic process / ATP hydrolysis activity / ATP binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Cricetus cricetus (black-bellied hamster) / Rattus norvegicus (Norway rat) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
Authors | Shyng SL / Sung MW / Driggers CM | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Elife / Year: 2019 Title: Mechanism of pharmacochaperoning in a mammalian K channel revealed by cryo-EM. Authors: Gregory M Martin / Min Woo Sung / Zhongying Yang / Laura M Innes / Balamurugan Kandasamy / Larry L David / Craig Yoshioka / Show-Ling Shyng / Abstract: ATP-sensitive potassium (K) channels composed of a pore-forming Kir6.2 potassium channel and a regulatory ABC transporter sulfonylurea receptor 1 (SUR1) regulate insulin secretion in pancreatic β- ...ATP-sensitive potassium (K) channels composed of a pore-forming Kir6.2 potassium channel and a regulatory ABC transporter sulfonylurea receptor 1 (SUR1) regulate insulin secretion in pancreatic β-cells to maintain glucose homeostasis. Mutations that impair channel folding or assembly prevent cell surface expression and cause congenital hyperinsulinism. Structurally diverse K inhibitors are known to act as pharmacochaperones to correct mutant channel expression, but the mechanism is unknown. Here, we compare cryoEM structures of a mammalian K channel bound to pharmacochaperones glibenclamide, repaglinide, and carbamazepine. We found all three drugs bind within a common pocket in SUR1. Further, we found the N-terminus of Kir6.2 inserted within the central cavity of the SUR1 ABC core, adjacent the drug binding pocket. The findings reveal a common mechanism by which diverse compounds stabilize the Kir6.2 N-terminus within SUR1's ABC core, allowing it to act as a firm 'handle' for the assembly of metastable mutant SUR1-Kir6.2 complexes. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26304.map.gz | 9.3 MB | EMDB map data format | |
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Header (meta data) | emd-26304-v30.xml emd-26304.xml | 19.5 KB 19.5 KB | Display Display | EMDB header |
Images | emd_26304.png | 131.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26304 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26304 | HTTPS FTP |
-Validation report
Summary document | emd_26304_validation.pdf.gz | 420.4 KB | Display | EMDB validaton report |
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Full document | emd_26304_full_validation.pdf.gz | 420 KB | Display | |
Data in XML | emd_26304_validation.xml.gz | 4.5 KB | Display | |
Data in CIF | emd_26304_validation.cif.gz | 5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26304 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26304 | HTTPS FTP |
-Related structure data
Related structure data | 7u1sMC 7tysC 7tytC 7u1eC 7u1qC 7u24C 7u2xC 7u6yC 7u7mC 7uaaC 7uqrC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_26304.map.gz / Format: CCP4 / Size: 10 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. generated in cubic-lattice coordinate | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.045 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
+Entire : KATP-RPG-ATP-SUR-out
+Supramolecule #1: KATP-RPG-ATP-SUR-out
+Supramolecule #2: Kir6.2
+Supramolecule #3: SUR1
+Macromolecule #1: ATP-sensitive inward rectifier potassium channel 11
+Macromolecule #2: ATP-binding cassette sub-family C member 8
+Macromolecule #4: ADENOSINE-5'-TRIPHOSPHATE
+Macromolecule #5: POTASSIUM ION
+Macromolecule #6: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
+Macromolecule #7: O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phospho...
+Macromolecule #8: PHOSPHATIDYLETHANOLAMINE
+Macromolecule #9: Repaglinide
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.6 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 28289 |
Initial angle assignment | Type: COMMON LINE |
Final angle assignment | Type: ANGULAR RECONSTITUTION |