Uncovering the [2Fe2S] domain movement in cytochrome bc(1) and its implications for energy conversion

In crystals of the key respiratory and photosynthetic electron transfer pro tein called ubihydroquinone:cytochrome (cyt) c oxidoreductase or cyt bc(1), the extrinsic [2Fe2S] cluster domain of its Fe-S subunit assumes several c onformations, suggesting that it may move during catalysis. Herein, using R hodobacter capsulatus mutants that have modifications in the hinge region o f this subunit, we were able to reveal this motion kinetically. Thus. the b c(1) complex (and possibly the homologous b(6)f complex in chloroplasts) em ploys the [2Fe2S] cluster domain as a device to shuttle electrons from ubih ydroquinone to cyt c(1) (or cyt f). We demonstrate that this domain movemen t is essential for cyt bc(1) function, because a mutant enzyme with a nonmo ving Fe-S subunit has no catalytic activity, and one with a slower movement has lower activity. This motion is apparently designed with a natural freq uency slow enough to assure productive Q(0) site charge separation but fast enough not to be rate limiting. These findings add the unprecedented funct ion of intracomplex electron shuttling to large-scale domain motions in pro teins and may well provide a target for cyt bc(1) antibiotics.