Heteromer formation of a long-chain prenyl diphosphate synthase from fission yeast Dps1 and budding yeast Coq1

FEBS J. 2008 Jul;275(14):3653-68. doi: 10.1111/j.1742-4658.2008.06510.x.

Abstract

Ubiquinone is an essential factor for the electron transfer system and is also a known lipid antioxidant. The length of the ubiquinone isoprenoid side-chain differs amongst living organisms, with six isoprene units in the budding yeast Saccharomyces cerevisiae, eight units in Escherichia coli and 10 units in the fission yeast Schizosaccharomyces pombe and in humans. The length of the ubiquinone isoprenoid is determined by the product generated by polyprenyl diphosphate synthases (poly-PDSs), which are classified into homodimer (i.e. octa-PDS IspB in E. coli) and heterotetramer [i.e. deca-PDSs Dps1 and D-less polyprenyl diphosphate synthase (Dlp1) in Sc. pombe and in humans] types. In this study, we characterized the hexa-PDS (Coq1) of S. cerevisiae to identify whether this enzyme was a homodimer (as in bacteria) or a heteromer (as in fission yeast). When COQ1 was expressed in an E. coli ispB disruptant, only hexa-PDS activity and ubiquinone-6 were detected, indicating that the expression of Coq1 alone results in bacterial enzyme-like functionality. However, when expressed in fission yeast Deltadps1 and Deltadlp1 strains, COQ1 restored growth on minimal medium in the Deltadlp1 but not Deltadps1 strain. Intriguingly, ubiquinone-9 and ubiquinone-10, but not ubiquinone-6, were identified and deca-PDS activity was detected in the COQ1-expressing Deltadlp1 strain. No enzymatic activity or ubiquinone was detected in the COQ1-expressing Deltadps1 strain. These results indicate that Coq1 partners with Dps1, but not with Dlp1, to be functional in fission yeast. Binding of Coq1 and Dps1 was demonstrated by coimmunoprecipitation, and the formation of a tetramer consisting of Coq1 and Dps1 was detected in Sc. pombe. Thus, Coq1 is functional when expressed alone in E. coli and in budding yeast, but is only functional as a partner with Dps1 in fission yeast. This unusual observation indicates that different folding processes or protein modifications in budding yeast/E. coli versus those in fission yeast might affect the formation of an active enzyme. These results provide important insights into the process of how PDSs have evolved from homo- to hetero-types.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • DNA, Complementary / isolation & purification
  • Dimethylallyltranstransferase / chemistry
  • Dimethylallyltranstransferase / genetics
  • Dimethylallyltranstransferase / metabolism*
  • Escherichia coli / genetics
  • Escherichia coli Proteins / genetics
  • Genetic Complementation Test
  • Molecular Sequence Data
  • Mutation
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Schizosaccharomyces / enzymology*
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Ubiquinone / biosynthesis
  • Ubiquinone / chemistry

Substances

  • DNA, Complementary
  • Escherichia coli Proteins
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces pombe Proteins
  • Ubiquinone
  • Dimethylallyltranstransferase