Widespread Distribution and Functional Specificity of the Copper Importer CcoA: Distinct Cu Uptake Routes for Bacterial Cytochrome c Oxidases

摘要: ABSTRACT Cytochrome c oxidases are members of the heme-copper oxidase superfamily. These enzymes have different subunits, cofactors, and primary electron acceptors, yet they all contain identical (CuB) binuclear centers within their catalytic subunits. The uptake delivery pathways CuB atom incorporated into this active site, where oxygen is reduced to water, not well understood. Our previous work with facultative phototrophic bacterium Rhodobacter capsulatus indicated that copper needed for site cbb3-type cytochrome (cbb3-Cox) imported cytoplasm by a major facilitator superfamily-type transporter, CcoA. In study, comparative genomic analysis CcoA orthologs in alphaproteobacterial genomes showed widespread among organisms frequently co-occurs oxidases. To define specificity activity, we investigated its function sphaeroides, close relative R. capsulatus contains both cbb3- aa3-Cox. Phenotypic, genetic, biochemical characterization mutants lacking absence, or even presence bypass suppressors, only production cbb3-Cox aa3-Cox was affected. We therefore concluded dedicated solely biogenesis, establishing distinct systems provide atoms sites these two similar findings illustrate large variety strategies employ ensure homeostasis fine control trafficking target cuproproteins under physiological conditions. IMPORTANCE aa3-type belong They membrane-integral catalyze reduction water hypoxic normoxic growth diverge terms subunit cofactor composition, share conserved subunit. show center from superfamily provided during biogenesis. This finding illustrates which fine-tune copper, an essential but toxic micronutrient.