Decoding cytochrome c oxidase biogenesis: New insights into copper trafficking

摘要: Acquisition, delivery and incorporation of metals to their respective metalloproteins are important cellular processes. These processes tightly controlled so that cells not exposed free metal concentrations would lead harmful oxidative damages. Cytochrome c oxidases (Cox) among these whose assembly activity involves Cu cofactor into catalytic subunits in addition the maturation other subunits. In this study, we focused on pathways acquisition by facultative phototroph Rhodobacter capsulatus for heme–Cu binuclear center its cbb3–type Cox (cbb3–Cox). Genetic screens identified a cbb3–Cox defective mutant requires Cu2+ supplement produce an active cbb3–Cox. Complementation using wild-type genomic libraries unveiled novel gene (ccoA) required biogenesis R. capsulatus. absence CcoA, content decreases, becomes defective. CcoA shows pronounced homology Major Facilitator Superfamily (MFS) type transporter proteins. Members family known transport small solutes or drugs, but far, no MFS protein was implicated biogenesis. order dissect mechanism isolated ΔccoA mutants were after Cu. Characterization genetic complementations revealed mutations cytochrome (CCM) genes. able grow photosynthetically contrary usual phenotype CCM genes deletion mutants. Here show directly involved trafficking CcoN production membrane bound Although study provides additional information about system capsulatus, presence exogenous still remains be identified. future, determination ccoA bypass will provide insights membrane-integral metalloproteins, hitherto unknown function(s) transporters bacterial acquisition. Degree Type Dissertation Name Doctor Philosophy (PhD) Graduate Group Biology First Advisor Fevzi Daldal