ClC Channels : Reading Eukaryotic Function through Prokaryotic Spectacles

It's a truism that structures are helpful for mechanistic understanding of protein function, and nowhere is this dictum better illustrated than with ClC-type Cl⁻ channels, a large molecular family found in virtually every type of cell in every biological niche. These channels, first observed over 20 yr ago (White and Miller, 1979; Miller, 1982), are now known from a barrage of knockout studies (Jentsch et al., 2002) to maintain the smooth operation of many varied physiological systems: skeletal muscle excitability, inhibitory interneuron responses, renal control of blood pressure, endosome acidification, and, well, the list goes on and on. Although the first ClC channel was cloned nearly 15 yr ago (Jentsch et al., 1990), our physical and mechanistic picture of these proteins at the molecular level languished at a frustrating level of murkiness until the first high-resolution structure...