Profile of Christopher Miller

摘要

For Christopher Miller, looking at a CLC transporter protein conjures images of peering down a double-barreled shotgun. With its twin channels, the evocative structure is characteristic of an unusual molecular family. CLC transporters are proteins, structurally similar to each other, that move chloride ions across cell membranes via surprisingly different mechanisms, either by ionic "leaks" through aqueous channels or by "pumping" the ion uphill by exchange with protons. Miller, elected to the National Academy of Sciences in 2007, has been studying these CLC proteins since before x-ray crystallography made it possible to see their structures. In his Inaugural Article (1) in this issue of PNAS, Miller presents evidence from a step-by-step investigation to determine whether the twin subunits in a CLC exchanger pump operate independently or cooperatively. Miller "straitjacketed" the protein, immobilizing the subunits relative to one another with disulfide linkages. This straitjacketing would cause failure of the pump if the two sides cooperated, but Miller shows that the pump continues to operate despite the restrictions.