Gating of the TrkH ion channel by its associated RCK protein TrkA

TrkH belongs to a superfamily of K + transport proteins required for growth of bacteria in low external K + concentrations. The crystal structure of TrkH from Vibrio parahaemolyticus showed that TrkH resembles a K + channel and may have a gating mechanism substantially different from K + channels. TrkH assembles with TrkA, a cytosolic protein comprising two RCK (regulate the conductance of K + ) domains, which are found in certain K + channels and control their gating. However, fundamental questions on whether TrkH is an ion channel and how it is regulated by TrkA remain unresolved. Here we show single-channel activity of TrkH that is upregulated by ATP via TrkA. We report two structures of the tetrameric TrkA ring, one in complex with TrkH and one in isolation, in which the ring assumes two markedly different conformations. These results suggest a mechanism for how ATP increases TrkH activity by inducing conformational changes in TrkA. Here it is shown that ion flux through the TrkH–TrkA complex is upregulated by ATP and downregulated by ADP; solving the X-ray crystal structures of the tetrameric TrkA ring in the absence and presence of TrkH suggests a mechanism by which ATP-induced conformational changes in TrkA augment the activity of TrkH. Bacterial potassium transporters characterized K + is essential for many physiological processes and must be concentrated in all living cells for their survival. In bacteria, K + uptake is mediated and regulated by SKT (superfamily of K + transporter) proteins. Two papers in this issue of Nature examine the structure and function of SKT proteins from different sub-families. Ming Zhou and colleagues present the electrophysiological and structural characterization of the complex formed by TrkH and its associated RCK protein, TrkA. Their study suggests a mechanism by which ATP-induced conformational changes in TrkA augment TrkH's activity. Joo Morais-Cabral and colleagues determined the X-ray crystal structure of a Ktr K + transporter; the structure of this KtrAB complex reveals how the dimeric membrane protein KtrB interacts with the cytosolic octameric KtrA regulatory protein.