An Isoprene Lipid-Binding Protein Promotes Eukaryotic Coenzyme Q Biosynthesis

Danielle C. Lohman, Deniz Aydin, Helaina C. Von Bank, Robert W. Smith, Vanessa Linke, Erin Weisenhorn, Molly T. McDevitt, Paul Hutchins, Emily M. Wilkerson, Benjamin Wancewicz, Jason Russell, Matthew S. Stefely, Emily T. Beebe, Adam Jochem, Joshua J. Coon, Craig A. Bingman, Matteo Dal Peraro, David J. Pagliarini

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The biosynthesis of coenzyme Q presents a paradigm for how cells surmount hydrophobic barriers in lipid biology. In eukaryotes, CoQ precursors—among nature's most hydrophobic molecules—must somehow be presented to a series of enzymes peripherally associated with the mitochondrial inner membrane. Here, we reveal that this process relies on custom lipid-binding properties of COQ9. We show that COQ9 repurposes the bacterial TetR fold to bind aromatic isoprenes with high specificity, including CoQ intermediates that likely reside entirely within the bilayer. We reveal a process by which COQ9 associates with cardiolipin-rich membranes and warps the membrane surface to access this cargo. Finally, we identify a molecular interface between COQ9 and the hydroxylase COQ7, motivating a model whereby COQ9 presents intermediates directly to CoQ enzymes. Overall, our results provide a mechanism for how a lipid-binding protein might access, select, and deliver specific cargo from a membrane to promote biosynthesis. Lipid metabolism and transport rely on proteins that operate at the membrane-water barrier and have dynamic interactions with membranes, lipids, and other proteins. Lohman et al. report mechanistic insights into how COQ9 might access, select, and present specific membrane cargo to a peripheral membrane enzyme during coenzyme Q biosynthesis.

Original languageEnglish
Pages (from-to)763-774.e10
JournalMolecular cell
Volume73
Issue number4
DOIs
StatePublished - Feb 21 2019

Keywords

  • coenzyme Q
  • lipid-binding protein
  • mitochondria
  • peripheral membrane protein

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