Structure-function relationships of integral membrane proteins: Membrane transporters vs channels

Escherichia coli lactose permease, a paradigm for membrane transport protei ns, and Streptomyces lividans KcsA, a paradigm for K+ channels, are compare d on the level of structure, dynamics, and function. The homotetrameric cha nnel, which allows the downhill movement of K+ with an electrochemical grad ient, is relatively rigid and inflexible, as observed by Fourier transform infrared spectroscopy. Lactose permease catalyzes transduction of free ener gy stored in an electrochemical H+ gradient into work in the form of a conc entration gradient. In marked contrast to KcsA, the permease exhibits a hig h degree of H/D exchange, in addition to enhanced sensitivity to lateral li pid packing pressure, thereby indicating that this symport protein is extre mely flexible and conformationally active. Finally, the differences between lactose permease and KcsA are discussed in the context of their specific f unctions with particular emphasis on differences between coupling in sympor t proteins and gating in channels. (C) 2001 John Wiley & Sons, Inc.