Molecular mechanism of chloride ion transport by CLC protein family, with Roderick MacKinnon
Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, New York, New York
My current research focus is on understanding molecular mechanisms of CLC proteins, ubiquitous membrane proteins that transport chloride ions across membranes. The CLC proteins are involved in various biological processes including regulation of membrane potential, electrolyte/fluid transport across epithelia, and control of intravesicular pH. Mutations in CLC genes cause many hereditary disorders in humans. An interesting aspect of the CLC family is that a common structural architecture seems to be used for both active and passive ion transport. Some CLCs are chloride channels, which provide a passive pore for chloride ion conduction, whereas others function as secondary active transporters that exchange two chloride ions for one proton. Despite recent advances in our understanding of their mechanisms, fundamental questions remain unanswered, especially regarding how exactly CLC transporters couple the transfer of chloride and proton ions and what leads to the mechanistic difference between the channels and transporters. In the MacKinnon lab, I use structural and functional approaches to address these questions.