A new member of the family of di-iron carboxylate proteins. Coq7 (clk-1), a membrane-bound hydroxylase involved in ubiquinone biosynthesis.
Ubiquinone (UQ) is an essential cofactor for respiratory metabolism. In yeast, mutation of the COQ7 gene results in the absence of UQ biosynthesis and demonstrates a role for this gene in the step leading to the hydroxylation of 5-demethoxyubiquinone. Intriguingly, the disruption of the corresponding gene in Caenorhabditis elegans, clk-1, results in a prolonged life span and a slowing of development. Because of the pleiotropic effect of this disruption, the small size of the protein, and the lack of obvious homology to other known hydroxylases, it has been suggested that Coq7 may be a regulatory or structural component in UQ biosynthesis, rather than acting as the hydroxylase per se. Here we identify Coq7 as belonging to a family of a di-iron containing oxidases/hydroxylases based on a conserved sequence motif for the iron ligands, supporting a direct function of Coq7 as a hydroxylase. We have cloned COQ7 from Pseudomonas aeruginosa and Thiobacillus ferrooxidans and show that indeed this gene complements an Escherichia coli mutant that lacks an unrelated 5-demethoxyubiquinone hydroxylase. Based on the similarities to other well studied di-iron carboxylate proteins, we propose a structural model for Coq7 as an interfacial integral membrane protein.
Stenmark
P
P
Department of Biochemistry and Biophysics, Stockholm University, Svante Arrhenius väg 12, S-106 91 Stockholm, Sweden.
Grünler
J
J
Mattsson
J
J
Sindelar
P J
PJ
Nordlund
P
P
Berthold
D A
DA
D000595:Amino Acid Sequence; D001665:Binding Sites; D029742:Caenorhabditis elegans Proteins; D002462:Cell Membrane / Q000201:enzymology*; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000201:enzymology; D007501:Iron / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000201:enzymology; D017386:Sequence Homology, Amino Acid; D013855:Thiobacillus / Q000201:enzymology; D013997:Time Factors; D014451:Ubiquinone / Q000096:biosynthesis*
C104339:CLK-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D014451:Ubiquinone; D007501:Iron; D006899:Mixed Function Oxygenases