Structural and functional studies of ion channels and transporters
Biological membranes serve as selective barriers by which cells (or subcellular organelles) maintain an internal environment different from outside. It is composed of an enclosing lipid bilayer and proteins embedded in the lipid bilayer (integral membrane proteins). Integral membrane proteins are responsible for selective permeation of key molecules and information transfer across the cell membranes while lipid bilayer acts as a barrier. Therefore integral membrane proteins are central to many important physiologies such as ion transport, signaling, and hormone regulation and have been major targets for drug development. However, the dearth of atomic resolution structures and mechanistic understanding of membrane proteins prevents potential drug development.
Amongst the many classes of membrane proteins, we are interested in a class of membrane protein known as ion channels. Ion channels catalyze selective ion permeation and open and close (gate) under many different conditions such as voltage, ligand, temperature, pH and mechanical tension. We are currently working on the mechanisms of ion channels that gate by voltage and temperature at the molecular level. To answer the questions, we take a multidisciplinary approach. 1) X-ray crystallography is used to visualize structures of ion channels in different conformations to give us insight into mechanism of ion permeation and gating. 2) Electrophysiology is used to understand the functional importance of interactions that were inferred from structural studies. 3) Biochemical and biophysical methods (Fluorescence or NMR) are used to understand the dynamic features of ion channels, which can complement crystallographic or electrophysiological approaches.