Abstract: Ion transport across the hydrophobic barrier of the cell membrane is central to life. Two major classes of membrane proteins – passive ion channels and active transporters – have evolved to catalyze ion transport across this barrier. The “CLC” family of membrane proteins is unique in that half of the members are ion channels (catalyzing downhill movement of chloride), while the other half are secondary active transporters that stoichiometrically exchange chloride for protons (harnessing the energy from movement of chloride to pump protons or vice versa). In this seminar, I will discuss the similarities and differences between CLC channel and transporter mechanisms, and I will describe my laboratory’s work to understand protein conformational change involved in these mechanisms. While published crystal structures reveal only small conformational changes involving side-chain rotations, our work combining spectroscopy, cross-linking, crystallography, and computation provides insight into global structural changes in CLC function.