The Structure of the KtrAB Potassium Transporter

Abstract

The Trk/Ktr/HKT superfamily of ion transporters in bacteria, archaea, fungi and plants includes key transporters involved in osmotic regulation, pH homeostasis and resistance to drought and high salinity. These ion transporters are closely related to the superfamily of tetrameric cation channels, which includes potassium, sodium and calcium channels. A structural relationship between these superfamilies is observed both at the level of the membrane protein, with a similar 4-fold architecture and also at the level of the regulatory protein, that harbors RCK (regulate conductance of K+) domains. Here we describe the crystal structure of a Ktr ion transporter from Bacillus subtilis, the KtrAB potassium transporter. The structure shows a homodimeric membrane protein, KtrB, assembled with a cytosolic octameric KtrA ring bound to ATP. Biochemical studies demonstrate that KtrA binds ATP and ADP and a comparison between the structures of the isolated full-length KtrA protein with ATP or ADP reveals a ligand dependent conformational change in the octameric ring. A 4-fold symmetrical KtrA ring is observed with ATP and a 2-fold symmetrical KtrA ring is observed with ADP. The asymmetrical conformational change of the KtrA regulatory ring together with its non-covalent interaction with the KtrB membrane protein, contrasts with what is described for ion channels, such as BK and MthK. Our study uncovers important differences between KtrAB K+ transporter and ion channels, providing novel insights on the mechanism of regulation of the superfamily of ion transporters.