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Yorodumi- PDB-6pza: Cryo-EM structure of the pancreatic beta-cell SUR1 bound to ATP a... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6pza | ||||||
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Title | Cryo-EM structure of the pancreatic beta-cell SUR1 bound to ATP and glibenclamide | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / KATP / SUR1 / GBC | ||||||
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 / inward rectifier potassium channel activity / ATPase-coupled monoatomic cation transmembrane transporter activity / nervous system process / regulation of monoatomic ion transmembrane transport / inorganic cation transmembrane transport / ankyrin binding / Ion homeostasis / response to ATP / response to testosterone / voltage-gated potassium channel activity / potassium ion import across plasma membrane / action potential / regulation of insulin secretion / potassium channel activity / intercalated disc / axolemma / ABC-type transporter activity / negative regulation of insulin secretion / potassium ion transmembrane transport / T-tubule / heat shock protein binding / positive regulation of protein localization to plasma membrane / potassium ion transport / acrosomal vesicle / regulation of membrane potential / response to ischemia / determination of adult lifespan / cellular response to glucose stimulus / sarcolemma / cellular response to nicotine / glucose metabolic process / nuclear envelope / response to estradiol / cellular response to tumor necrosis factor / presynaptic membrane / transmembrane transporter binding / endosome / response to hypoxia / 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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.74 Å | ||||||
Authors | Shyng, S.L. / Yoshioka, C. / Martin, G.M. / Sung, M.W. | ||||||
Funding support | United States, 1items
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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
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6pza.cif.gz | 251.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6pza.ent.gz | 190.1 KB | Display | PDB format |
PDBx/mmJSON format | 6pza.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6pza_validation.pdf.gz | 845 KB | Display | wwPDB validaton report |
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Full document | 6pza_full_validation.pdf.gz | 851.3 KB | Display | |
Data in XML | 6pza_validation.xml.gz | 38.6 KB | Display | |
Data in CIF | 6pza_validation.cif.gz | 60.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pz/6pza ftp://data.pdbj.org/pub/pdb/validation_reports/pz/6pza | HTTPS FTP |
-Related structure data
Related structure data | 20530MC 6pz9C 6pzbC 6pzcC 6pziC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 177333.578 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Cricetus cricetus (black-bellied hamster) Gene: ABCC8, SUR / Production host: Rattus norvegicus (Norway rat) / References: UniProt: Q09427 |
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#2: Protein | Mass: 43645.719 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Kcnj11 / Production host: Rattus norvegicus (Norway rat) / References: UniProt: P70673 |
#3: Chemical | ChemComp-GBM / |
#4: Chemical | ChemComp-ATP / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Details: unspecified | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-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: 40 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: NONE | |||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||
3D reconstruction | Resolution: 3.74 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 171420 / Symmetry type: POINT | |||||||||
Atomic model building | PDB-ID: 6BAA |