Microscopy Club Lecture

Membrane proteins perform key functions in living cells and the knowledge of their structure is critically important for the understanding of their function. Native lipids, transmembrane gradients, interacting partners modulate structure and function of membrane proteins in physiological settings and are often lost during the preparation of the channels for structural analysis. During the talk I will discuss the mechanisms of activation of ion channels that we analyze using the modern arsenal of cryo-EM methods. First, I will show our structure of the serotonin receptor ion channel that we determined in membrane memetics ^[1] and will compare the activation mechanism to the previously suggested. I will then discuss the potential of in situ structural biology of membrane proteins using cryo electron tomography and subtomogram averaging and will demonstrate its applications to ion channels. Notably, I will discuss the impact that native lipids have on the structure of ion channels using the giant calcium channel RyR1 from rabbit muscle ^{[2, 3]} and will discuss the potential to obtain more informative structures in native membranes.