From ions to insulin

Abstract

Electron cryo-microscopy has revealed the three-dimensional structure of a potassium channel that has a central role in regulating the release of insulin from the pancreas.

Keywords: ABC transporter; biophysics; inward rectifier; none; structural biology; sulfonylurea; sulfonylurea receptor.

Figure 1.. Schematic diagrams of a closed K_ATP channel.

Each K_ATP channel contains four Kir6.2 subunits (green) and four SUR1 subunits. Each SUR1 subunit contains a core (blue), an L0 linker (purple line) and a transmembrane domain called TMD0 (purple). The diagrams are based on the cryo-EM K_ATP channel structures by Martin et al. and Li et al. (A) Top view of the channel showing the propeller-shaped structure. (B) Side view of the channel showing two Kir6.2 subunits and two SUR1 subunits sitting in the cell membrane (gray). The core of SUR1 contains two transmembrane domains (TMD1 and TMD2) and two nucleotide-binding domains (NBD1 and NBD2), while the L0 linker contains two short α-helices. The Kir6.2 subunit is made of two transmembrane helices (dark green rectangle) and two cytoplasmic regions (light green rectangle). Martin et al. and Li et al. found that the center of the K_ATP channel propeller structure is formed by the Kir6.2 subunits and the TMD0 of SUR1. The cores of the SUR1 subunits form the propeller blades, but there are unexpected spaces between the cores of adjacent SUR1 subunits that had not been observed in a previously reported structure formed under different conditions (Mikhailov et al., 2005).