+Open data
-Basic information
Entry | Database: PDB / ID: 6jb3 | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of SUR1 subunit bound with repaglinide | |||||||||||||||
Components | ATP-binding cassette sub-family C member 8 isoform X2 | |||||||||||||||
Keywords | MEMBRANE PROTEIN / KATP / channel / repaglinide / Kir / ABC transporter / SUR / diabetes / insulin secretagogue | |||||||||||||||
Function / homology | Function and homology information glutamate secretion, neurotransmission / inward rectifying potassium channel / sulfonylurea receptor activity / ATPase-coupled monoatomic cation transmembrane transporter activity / inorganic cation transmembrane transport / neuromuscular process / positive regulation of insulin secretion involved in cellular response to glucose stimulus / potassium channel activity / ABC-type transporter activity / negative regulation of insulin secretion ...glutamate secretion, neurotransmission / inward rectifying potassium channel / sulfonylurea receptor activity / ATPase-coupled monoatomic cation transmembrane transporter activity / inorganic cation transmembrane transport / neuromuscular process / positive regulation of insulin secretion involved in cellular response to glucose stimulus / potassium channel activity / ABC-type transporter activity / negative regulation of insulin secretion / ADP binding / presynapse / transmembrane transporter binding / ATP hydrolysis activity / ATP binding Similarity search - Function | |||||||||||||||
Biological species | Mesocricetus auratus (golden hamster) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.53 Å | |||||||||||||||
Authors | Chen, L. / Ding, D. / Wang, M. / Wu, J.-X. / Kang, Y. | |||||||||||||||
Funding support | China, 4items
| |||||||||||||||
Citation | Journal: Cell Rep / Year: 2019 Title: The Structural Basis for the Binding of Repaglinide to the Pancreatic K Channel. Authors: Dian Ding / Mengmeng Wang / Jing-Xiang Wu / Yunlu Kang / Lei Chen / Abstract: Repaglinide (RPG) is a short-acting insulin secretagogue widely prescribed for the treatment of type 2 diabetes. It boosts insulin secretion by inhibiting the pancreatic ATP-sensitive potassium ...Repaglinide (RPG) is a short-acting insulin secretagogue widely prescribed for the treatment of type 2 diabetes. It boosts insulin secretion by inhibiting the pancreatic ATP-sensitive potassium channel (K). However, the mechanisms by which RPG binds to the K channel are poorly understood. Here, we describe two cryo-EM structures: the pancreatic K channel in complex with inhibitory RPG and adenosine-5'-(γ-thio)-triphosphate (ATPγS) at 3.3 Å and a medium-resolution structure of a RPG-bound mini SUR1 protein in which the N terminus of the inward-rectifying potassium channel 6.1 (Kir6.1) is fused to the ABC transporter module of the sulfonylurea receptor 1 (SUR1). These structures reveal the binding site of RPG in the SUR1 subunit. Furthermore, the high-resolution structure reveals the complex architecture of the ATP binding site, which is formed by both Kir6.2 and SUR1 subunits, and the domain-domain interaction interfaces. | |||||||||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6jb3.cif.gz | 168.4 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6jb3.ent.gz | 117.4 KB | Display | PDB format |
PDBx/mmJSON format | 6jb3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6jb3_validation.pdf.gz | 872.5 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 6jb3_full_validation.pdf.gz | 886.8 KB | Display | |
Data in XML | 6jb3_validation.xml.gz | 30.6 KB | Display | |
Data in CIF | 6jb3_validation.cif.gz | 44.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jb/6jb3 ftp://data.pdbj.org/pub/pdb/validation_reports/jb/6jb3 | HTTPS FTP |
-Related structure data
Related structure data | 9788MC 9787C 9789C 6jb1C M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 177295.516 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mesocricetus auratus (golden hamster) / Gene: Abcc8 / Production host: Homo sapiens (human) / References: UniProt: A0A1U7R319 |
---|---|
#2: Chemical | ChemComp-BJX / |
#3: Chemical | ChemComp-AJP / |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: SUR1 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: Mus musculus (house mouse) |
Source (recombinant) | Organism: Homo sapiens (human) |
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 |
---|---|
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: 50 e/Å2 / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: (1.12_2829: ???) / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software | Name: RELION / Version: 2 / Category: 3D reconstruction | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CTF correction | Type: NONE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.53 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 653991 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | Resolution: 3.53→3.53 Å / SU ML: 1.4 / σ(F): 0.01 / Phase error: 64.36 / Stereochemistry target values: MLHL
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
|