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An Isoprene Lipid-Binding Protein Promotes Eukaryotic Coenzyme Q Biosynthesis

Journal Article · · Molecular Cell
 [1];  [2];  [3];  [4];  [4];  [4];  [4];  [5];  [4];  [4];  [6];  [1];  [4];  [3];  [7];  [1];  [2];  [1]
  1. Morgridge Inst. for Research, Madison, WI (United States); Univ. of Wisconsin, Madison, WI (United States)
  2. Ecole Polytechnique Federale Lausanne (EPFL), Lausanne (Switzlerland)
  3. Morgridge Inst. for Research, Madison, WI (United States)
  4. Univ. of Wisconsin, Madison, WI (United States)
  5. Univ. of Wisconsin, Madison, WI (United States); Genome Center of Wisconsin, Madison, WI (United States)
  6. Morgridge Inst. for Research, Madison, WI (United States); Genome Center of Wisconsin, Madison, WI (United States)
  7. Morgridge Inst. for Research, Madison, WI (United States); Univ. of Wisconsin, Madison, WI (United States); Genome Center of Wisconsin, Madison, WI (United States)

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 in this paper, 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.

Research Organization:
Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
Sponsoring Organization:
USDOE Office of Science (SC); National Institutes of Health (NIH); National Science Foundation (NSF); Swiss National Science Foundation (SNSF)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1497168
Journal Information:
Molecular Cell, Journal Name: Molecular Cell Journal Issue: 4 Vol. 73; ISSN 1097-2765
Publisher:
Cell Press - ElsevierCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Cited By (3)

A fatal case of COQ7 ‐associated primary coenzyme Q 10 deficiency journal April 2019
The role of lipids in α-synuclein misfolding and neurotoxicity journal May 2019
Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER–mitochondria contacts journal January 2019

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