Cytochrome-c oxidase. Subunit structure and proton pumping

Abstract

This article reviews the significance of the subunit structure of cytochrome‐c oxidase in proton pumping and in particular summarizes available evidences for or against a role of subunit III in the control of this important function of the enzyme.

Subunit III of cytochrome c oxidase is not involved in proton translocation: a site-directed mutagenesis study.

“…The functional role of COIm has remained enigmatic: its removal from the purified enzyme does not have a large effect on the electron transfer or on the structure of the redox centres located in COI and COIl. However, and most importantly, the removal of COIII invariably brings about a significant reduction in the proton translocation efficiency of the bovine enzyme (for reviews, see Prochaska and Fink, 1987;Brunori et al, 1987). COHI contains a conserved glutamic acid residue (E98 in P. denitrificans) in the middle of a hydrophobic sequence that is likely to form a membrane-spanning helix (Raitio et al, 1987;see Figure 1).…”

“…Our results imply that the search for protein structures involved in this activity should focus on COI and COIl, and that the more than ten years of speculation about a role of COUI in proton pumping (Casey et al, 1980;Prochaska et al, 1981;Wikstrom and Casey, 1985;Capitanio et al, 1990;Prochaska and Wilson, 1990; for reviews, see Azzi et al, 1984;Brunori et al, 1987;Prochaska and Fink, 1987;Chan and Li, 1990) should come to an end. COIII has a distinct role in the assembly of the functional oxidase (for other assembly factors needed at earlier stages of oxidase biosynthesis, see Nobrega et al, 1990;Tzagoloff et al, 1990;Steinrucke et al, 1991).…”

“…For example, the CUA site in COIH becomes more prone to a structural perturbation (Li et al, 1988 might influence proton translocation indirectly by affecting the conformation of the rest of the enzyme. Removal of COIII from the assembled enzyme may, on this basis, be thought to destabilize the COI-COIl complex, the first sign of which may be a slipping proton pump with a lower H+/e-ratio (Brunori et al, 1987;Prochaska and Fink, 1987;Prochaska and Wilson, 1990). Finally, careful inspection of Figure 3 reveals that the E98 and D259 mutants may have slightly elevated levels of free COI (cf.…”

“…The total (Penttila, 1983) or partial (see Solioz et al, 1982;Brunori et al, 1987;Prochaska and Fink, 1987) loss of proton pumping activity upon removal of COIII from the isolated enzyme must be ascribed to a secondary structural perturbation of the COI-COII complex. The inhibition of proton pumping by DCCD (Casey et al, 1980;Prochaska et al, 1981) may, analogously, be due to a perturbation resulting from the introduction of a bulky dicyclohexyl residue to a membrane-spanning segment of COIII.…”

Molecular characterization of a mitochondrial mutant carrying point mutations in the 3′ untranslated region of theCOX3mRNA fromSaccharomyces cerevisiae

“…Because no metal centers are associated with subunit III, it is unlikely to function directly in electron transfer. Previous reports favor a role for subunit III in the proton pumping functions of the holoenzyme (Thompson et al 1985;Brunori et al 1987;Prochaska & Fink 1987;Wilson & Prochaska 1990;Hosler 2004) or in holoenzyme stability (Meunier & Taanman 2002).…”