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Yorodumi- PDB-6baa: Cryo-EM structure of the pancreatic beta-cell KATP channel bound ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6baa | ||||||
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Title | Cryo-EM structure of the pancreatic beta-cell KATP channel bound to ATP and glibenclamide | ||||||
Components |
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Keywords | METAL TRANSPORT / KATP / SUR1 / Kir6.2 / sulfonylurea receptor | ||||||
Function / homology | Function and homology information Regulation of insulin secretion / ATP sensitive Potassium channels / ABC-family proteins mediated transport / response to resveratrol / ventricular cardiac muscle tissue development / ATP-activated inward rectifier potassium channel activity / cell body fiber / inward rectifying potassium channel / sulfonylurea receptor activity / CAMKK-AMPK signaling cascade ...Regulation of insulin secretion / ATP sensitive Potassium channels / ABC-family proteins mediated transport / response to resveratrol / ventricular cardiac muscle tissue development / ATP-activated inward rectifier potassium channel activity / cell body fiber / inward rectifying potassium channel / sulfonylurea receptor activity / 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 / action potential / ankyrin binding / Ion homeostasis / response to ATP / response to testosterone / potassium ion import across plasma membrane / voltage-gated potassium channel activity / potassium channel activity / regulation of insulin secretion / axolemma / intercalated disc / negative regulation of insulin secretion / ABC-type transporter activity / potassium ion transmembrane transport / T-tubule / heat shock protein binding / regulation of membrane potential / acrosomal vesicle / response to ischemia / determination of adult lifespan / positive regulation of protein localization to plasma membrane / cellular response to glucose stimulus / sarcolemma / potassium ion transport / 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 | Rattus norvegicus (Norway rat) Cricetus cricetus (black-bellied hamster) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.63 Å | ||||||
Authors | Martin, G.M. / Yoshioka, C. / Shyng, S.L. | ||||||
Funding support | United States, 1items
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Citation | Journal: Elife / Year: 2017 Title: Anti-diabetic drug binding site in a mammalian K channel revealed by Cryo-EM. Authors: Gregory M Martin / Balamurugan Kandasamy / Frank DiMaio / Craig Yoshioka / Show-Ling Shyng / Abstract: Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic K channels composed of SUR1 and Kir6.2. The mechanism by which these drugs interact with and inhibit the channel has been ...Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic K channels composed of SUR1 and Kir6.2. The mechanism by which these drugs interact with and inhibit the channel has been extensively investigated, yet it remains unclear where the drug binding pocket resides. Here, we present a cryo-EM structure of a hamster SUR1/rat Kir6.2 channel bound to a high-affinity sulfonylurea drug glibenclamide and ATP at 3.63 Å resolution, which reveals unprecedented details of the ATP and glibenclamide binding sites. Importantly, the structure shows for the first time that glibenclamide is lodged in the transmembrane bundle of the SUR1-ABC core connected to the first nucleotide binding domain near the inner leaflet of the lipid bilayer. Mutation of residues predicted to interact with glibenclamide in our model led to reduced sensitivity to glibenclamide. Our structure provides novel mechanistic insights of how sulfonylureas and ATP interact with the K channel complex to inhibit channel activity. | ||||||
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 | 6baa.cif.gz | 1 MB | Display | PDBx/mmCIF format |
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PDB format | pdb6baa.ent.gz | 832.3 KB | Display | PDB format |
PDBx/mmJSON format | 6baa.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ba/6baa ftp://data.pdbj.org/pub/pdb/validation_reports/ba/6baa | HTTPS FTP |
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-Related structure data
Related structure data | 7073MC 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: 43645.719 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Kcnj11 / Cell line (production host): INS-1 / Production host: Rattus norvegicus (Norway rat) / References: UniProt: P70673 #2: Protein | Mass: 177333.578 Da / Num. of mol.: 4 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 #3: Chemical | ChemComp-ATP / #4: Chemical | ChemComp-GBM / |
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-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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Molecular weight | Value: 0.95 MDa / Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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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 | ||||||||||||||||||||||||
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 FIELDBright-field microscopy |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Symmetry | Point symmetry: C4 (4 fold cyclic) |
3D reconstruction | Resolution: 3.63 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 59417 / Symmetry type: POINT |