We are studying the newly discovered phenomenon of lipid-dependent gating of voltage-gated ion channels. We use cryoEM imaging of individual molecules and 2D crystals of membrane proteins to determine the structures of membrane proteins, and insert these channel proteins into lipid bilayers to study their functions in membranes.
Our working hypothesis is that the lipid-voltage sensor interaction changes the energetics of the protein between two of main conformational states of the voltage sensor.
We are also interested in the structural studies of inositol 1,4,5-trisphosphate receptors (IP3Rs). We prepare recombinant receptors to biochemical homogeneity and maintain them in different gating conformations for cryoEM imaging and single-particle reconstruction.
The structural coupling between ligand-binding and the pore opening will deliver new insights on the control of the ion channel pore. It will set up the stage to study the effects of multiple cellular factors that regulate IP3R activity and intracellular calcium signaling.