|Entry||Database: EMDB / ID: EMD-9789|
|Title||Structure of a SUR1 fusion protein|
|Sample||KATPATP-sensitive potassium channel|
|Biological species||Mus musculus (house mouse)|
|Method||single particle reconstruction / cryo EM / Resolution: 6.45 Å|
|Authors||Chen L / Ding D / Wang M / Wu J-X / Kang Y|
|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.
|Structure viewer||EM map: |
Downloads & links
|File||Download / File: emd_9789.map.gz / Format: CCP4 / Size: 12.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)|
|Projections & slices|
Images are generated by Spider.
|Voxel size||X=Y=Z: 1.636 Å|
|Symmetry||Space group: 1|
CCP4 map header:
|Entire||Name: KATPATP-sensitive potassium channel / Number of components: 1|
-Component #1: protein, KATP
|Protein||Name: KATPATP-sensitive potassium channel / Recombinant expression: No|
|Source||Species: Mus musculus (house mouse)|
|Source (engineered)||Expression System: Homo sapiens (human)|
|Specimen||Specimen state: Particle / Method: cryo EM|
|Sample solution||pH: 7.5|
|Vitrification||Cryogen name: ETHANE|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Imaging||Microscope: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Electron dose: 50 e/Å2 / Illumination mode: FLOOD BEAM|
|Lens||Imaging mode: BRIGHT FIELD|
|Specimen Holder||Model: OTHER|
|Camera||Detector: GATAN K2 QUANTUM (4k x 4k)|
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