Gating of bacterial transporters and ion channels involved in cellular homeostasis. (360G-Wellcome-077564_B_05_Z)

We have established that bacterial cells require cellular homeostasis for growth and survival in diverse niches. Ion channels play major roles in cellular homeostasis, as exemplified by our previous work on mechanogated (MscS & MscK) and electrophile-activated (KefC) channels. We have made considerable progress in understanding the gating of these two channel types and the future programme will concentrate specifically on the gating transitions in the channels. Additionally, we will pursue high resolution structures for the closed state of both MscS and MscK and assess important regions of the KefC structure in order to link them to function. The team members have become expert in electrophysiology, molecular genetics and protein biochemistry and they have made significant contributions to understanding the mechanisms and physiological roles of bacterial ion channels. The programme builds on these core skills, which will be augmented by strategic structural and biophysical collaborations (Naismith & Perozo). The key objectives will be: Detailed understanding of the gating transition of the MscS and MscK channels. Closed structures for MscS and MscK. Structural analysis of KefC - definition of the ion translocation pathway and the gating transition.