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The START domain Coq10 polypeptide binds Coenzyme Q and is required for mitochondrial respiratory electron transport
Author(s) -
Morvaridi Susan,
Saiki Ryoichi,
Liau WeiSiang,
Kawashima Tadashi,
Clarke Cathy
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.697.2
Subject(s) - coenzyme q – cytochrome c reductase , mutant , biology , biochemistry , saccharomyces cerevisiae , mitochondrion , cofactor , respiratory chain , mutagenesis , inner mitochondrial membrane , gene , enzyme , cytochrome c
Coenzyme Q (Q) is a redox active lipid that is an essential component of the electron transport chain in the mitochondrial membrane. In Saccharomyces cerevisiae , ten COQ genes are required for Q biosynthesis and function in respiratory electron transport. Nine genes are required for synthesis of Q, COQ1 through COQ9. However, unlike the other coq mutants, each of which lack Q 6 , the coq10 mutant has near normal amounts of Q 6 in mitochondria. The defect in oxidation of NADH and succinate in coq10 mutant mitochondria can be rescued by the addition of Q 2 , a water soluble analog. Coq10p is widely distributed in bacteria and eukaryotes and is homologous to proteins of the "aromatic‐rich protein family" Pfam03654. The structure of the Caulobacter crescentus Coq10 homolog, CC1736, identified it as a member of the START domain superfamily. The START domain containes a hydrophobic cavity that binds lipophilic molecules such as cholesterol or polyketides. Our data show that expression of C. crescentus CC1736 is able to rescue the respiratory deficiency of the yeast coq10 null mutant. The rescue depends on the presence of a mitochondrial leader sequence. An assay of Q binding shows that purified CC1736 is able to bind Q 10, Q 6 and Q 2 in molar ratio near to one. Site directed mutagenesis shows that Valine 70 of CC1736 is crucial for both rescue of the coq10 mutant and the coenzyme Q10 binding. The results suggest that the Coq10 polypeptide:coenzyme Q, protein:ligand complex may serve an essential function in the delivery of Q from its site of synthesis in the inner mitochondrial membrane to the respiratory electron transport chain.