Structural Basis of Redox coupled Protein Substrate Selection by the Cytochrome c Biosynthesis Protein ResA

Abstract

Post translational maturation of cytochromes c involves the covalent attachment of heme to the Cys Xxx Xxx Cys His motif of the apo cytochrome. For this process, the two cysteines of the motif must be in the reduced state. In bacteria, this is achieved by dedicated, membrane bound thiol disulfide oxidoreductases with a high reducing power, which are essential components of cytochrome c maturation systems and are also linked to cellular disulfide bond formation machineries. Here we report high resolution structures of oxidized and reduced states of a soluble, functional domain of one such oxidoreductase, ResA, from Bacillus subtilis. The structures elucidate the structural basis of the protein s high reducing power and reveal the largest redox coupled conformational changes observed to date in any thioredoxin like protein. These redox coupled changes alter the protein surface and illustrate how the redox state of ResA predetermines to which substrate it binds. Furthermore, a polar cavity, present only in the reduced state, may confer specificity to recognize apo cytochrome c. The described features of ResA are likely to be general for bacterial cytochrome c maturation system