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Mol Cell. 2019 Feb 21;73(4):763-774.e10. doi: 10.1016/j.molcel.2018.11.033. Epub 2019 Jan 17.

An Isoprene Lipid-Binding Protein Promotes Eukaryotic Coenzyme Q Biosynthesis.

Author information

1
Morgridge Institute for Research, Madison, WI 53715, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53715, USA.
2
Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
3
Morgridge Institute for Research, Madison, WI 53715, USA.
4
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53715, USA.
5
Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53715, USA.
6
Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53715, USA.
7
Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53715, USA; Genome Center of Wisconsin, Madison, WI 53715, USA.
8
Morgridge Institute for Research, Madison, WI 53715, USA; Genome Center of Wisconsin, Madison, WI 53715, USA.
9
Morgridge Institute for Research, Madison, WI 53715, USA; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53715, USA; Genome Center of Wisconsin, Madison, WI 53715, USA.
10
Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address: matteo.dalperaro@epfl.ch.
11
Morgridge Institute for Research, Madison, WI 53715, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53715, USA. Electronic address: dpagliarini@morgridge.org.

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.

KEYWORDS:

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

PMID:
30661980
PMCID:
PMC6386619
[Available on 2020-02-21]
DOI:
10.1016/j.molcel.2018.11.033
[Indexed for MEDLINE]

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