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- EMDB-26193: Cryo-EM structure of the pancreatic ATP-sensitive potassium chann... -
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Open data
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Basic information
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Title | Cryo-EM structure of the pancreatic ATP-sensitive potassium channel bound to ATP and repaglinide with Kir6.2-CTD in the up conformation | |||||||||
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Function / homology | ![]() 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 / inward rectifier potassium channel activity / ATPase-coupled monoatomic cation transmembrane transporter activity / regulation of monoatomic ion transmembrane transport / inorganic cation transmembrane transport / nervous system process / ankyrin binding / action potential / response to ATP / Ion homeostasis / response to testosterone / voltage-gated potassium channel activity / potassium channel activity / potassium ion import across plasma membrane / regulation of insulin secretion / intercalated disc / axolemma / negative regulation of insulin secretion / ABC-type transporter activity / potassium ion transmembrane transport / T-tubule / heat shock protein binding / acrosomal vesicle / response to ischemia / regulation of membrane potential / determination of adult lifespan / cellular response to glucose stimulus / positive regulation of protein localization to plasma membrane / potassium ion transport / sarcolemma / cellular response to nicotine / glucose metabolic process / response to estradiol / presynaptic membrane / nuclear envelope / cellular response to tumor necrosis factor / 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 | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.41 Å | |||||||||
![]() | Shyng SL / Sung MW / Driggers CM | |||||||||
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![]() | ![]() 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 | ![]() | 9.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 18.9 KB 18.9 KB | Display Display | ![]() |
Images | ![]() | 87.9 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 412.6 KB | Display | ![]() |
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Full document | ![]() | 412.1 KB | Display | |
Data in XML | ![]() | 4.6 KB | Display | |
Data in CIF | ![]() | 5.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7tysMC ![]() 7tytC ![]() 7u1eC ![]() 7u1qC ![]() 7u1sC ![]() 7u24C ![]() 7u2xC ![]() 7u6yC ![]() 7u7mC ![]() 7uaaC ![]() 7uqrC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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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
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Sample components
+Entire : KATP-RPG-ATP-CTDup
+Supramolecule #1: KATP-RPG-ATP-CTDup
+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: (9R,12R)-15-amino-12-hydroxy-6,12-dioxo-7,11,13-trioxa-12lambda~5...
+Macromolecule #9: Repaglinide
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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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: ![]() |
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 |
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Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.41 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 64405 |
Initial angle assignment | Type: COMMON LINE |
Final angle assignment | Type: ANGULAR RECONSTITUTION |