Molecular structure of human KATP in complex with ATP and ADP.

ABSTRACT: In many excitable cells, KATP channels respond to intracellular adenosine nucleotides: ATP inhibits while ADP activates. We present two structures of the human pancreatic KATP channel, containing the ABC transporter SUR1 and the inward-rectifier K⁺ channel Kir6.2, in the presence of Mg²⁺ and nucleotides. These structures, referred to as quatrefoil and propeller forms, were determined by single-particle cryo-EM at 3.9 Å and 5.6 Å, respectively. In both forms, ATP occupies the inhibitory site in Kir6.2. The nucleotide-binding domains of SUR1 are dimerized with Mg²⁺-ATP in the degenerate site and Mg²⁺-ADP in the consensus site. A lasso extension forms an interface between SUR1 and Kir6.2 adjacent to the ATP site in the propeller form and is disrupte

SUBMITTER: Lee KPK 

PROVIDER: S-EPMC5790381 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature