title: A conserved START domain coenzyme Q-binding polypeptide is required for efficient Q biosynthesis, respiratory electron transport, and antioxidant function in Saccharomyces cerevisiae.
abstract: Coenzyme Qn (ubiquinone or Qn) is a redox active lipid composed of a fully substituted benzoquinone ring and a polyisoprenoid tail of n isoprene units. Saccharomyces cerevisiae coq1-coq9 mutants have defects in Q biosynthesis, lack Q6, are respiratory defective, and sensitive to stress imposed by polyunsaturated fatty acids. The hallmark phenotype of the Q-less yeast coq mutants is that respiration in isolated mitochondria can be rescued by the addition of Q2, a soluble Q analog. Yeast coq10 mutants share each of these phenotypes, with the surprising exception that they continue to produce Q6. Structure determination of the Caulobacter crescentus Coq10 homolog (CC1736) revealed a steroidogenic acute regulatory protein-related lipid transfer (START) domain, a hydrophobic tunnel known to bind specific lipids in other START domain family members. Here we show that purified CC1736 binds Q2, Q3, Q10, or demethoxy-Q3 in an equimolar ratio, but fails to bind 3-farnesyl-4-hydroxybenzoic acid, a farnesylated analog of an early Q-intermediate. Over-expression of C. crescentus CC1736 or COQ8 restores respiratory electron transport and antioxidant function of Q6 in the yeast coq10 null mutant. Studies with stable isotope ring precursors of Q reveal that early Q-biosynthetic intermediates accumulate in the coq10 mutant and de novo Q-biosynthesis is less efficient than in the wild-type yeast or rescued coq10 mutant. The results suggest that the Coq10 polypeptide:Q (protein:ligand) complex may serve essential functions in facilitating de novo Q biosynthesis and in delivering newly synthesized Q to one or more complexes of the respiratory electron transport chain.
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Allan
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors.forename: Shauna
authors.initials: S
authors.lastname: Hill
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors.forename: Susan
authors.initials: S
authors.lastname: Morvaridi
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Saiki
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors.forename: Jarrett S
authors.initials: JS
authors.lastname: Johnson
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors.forename: Wei-Siang
authors.initials: WS
authors.lastname: Liau
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Hirano
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kawashima
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Ji
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Loo
authors.affiliation: Department of Chemistry and Biochemistry, Gonzaga University, Spokane, WA 99258.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Shepherd
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors.forename: Catherine F
authors.initials: CF
authors.lastname: Clarke
mesh_terms: D000595:Amino Acid Sequence; D000975:Antioxidants / Q000378:metabolism*; D004579:Electron Transport / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D014451:Ubiquinone; C024989:coenzyme Q10