@article{d3070a9ad67d457fb6a74856bdb05046,
title = "An Isoprene Lipid-Binding Protein Promotes Eukaryotic Coenzyme Q Biosynthesis",
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.",
keywords = "coenzyme Q, lipid-binding protein, mitochondria, peripheral membrane protein",
author = "Lohman, {Danielle C.} and Deniz Aydin and {Von Bank}, {Helaina C.} and Smith, {Robert W.} and Vanessa Linke and Erin Weisenhorn and McDevitt, {Molly T.} and Paul Hutchins and Wilkerson, {Emily M.} and Benjamin Wancewicz and Jason Russell and Stefely, {Matthew S.} and Beebe, {Emily T.} and Adam Jochem and Coon, {Joshua J.} and Bingman, {Craig A.} and {Dal Peraro}, Matteo and Pagliarini, {David J.}",
note = "Funding Information: We thank members of the Pagliarini Laboratory and Alessio Prunotto for helpful discussions, as well as Amy Lin for her assistance with figure generation. Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award numbers R01GM115591 (to D.J.P.), T32GM08349 (to D.C.L.), and R35GM118110 and P41GM108538 (to J.J.C.). This work was further supported by National Science Foundation Graduate Research Fellowship DGE-1256259 (to D.C.L.) and the Swiss National Science Foundation (grant 31003A_170154 to M.D.P.). Crystallization studies were performed at the Collaborative Crystallography Core in the Department of Biochemistry at the University of Wisconsin—Madison (C3DB). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Use of the LS-CAT Sector 21 was supported by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor (Grant 085P1000817 ). GM/CA@APS has been funded in whole or in part with Federal funds from the National Cancer Institute ( ACB-12002 ) and the National Institute of General Medical Sciences ( AGM-12006 ). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2019",
month = feb,
day = "21",
doi = "10.1016/j.molcel.2018.11.033",
language = "English",
volume = "73",
pages = "763--774.e10",
journal = "Molecular Cell",
issn = "1097-2765",
number = "4",
}