Structural Basis of Mitochondrial Scaffolds by Prohibitin Complexes: Implications for Mitochondrial-Mediated Antiviral Innate Immunity
59 Pages Posted: 26 Feb 2019 Sneak Peek Status: Review CompleteMore...
The coiled-coil motif mediates subunit oligomerization and scaffolding, and underlies several fundamental biologic processes. Prohibitins (PHBs), mitochondrial inner membrane proteins involved in mitochondrial homeostasis and signal transduction, are predicted to have a coiled-coil motif, but their structural features are poorly understood. Here we solved the crystal structure of the heptad repeat (HR) region of PHB2 at 1.7 Å resolution. It assembles into a dimeric, antiparallel coiled-coil with a unique negatively charged area essential for the PHB interactome in mitochondria. Disruption of the HR coiled-coil prevents well-ordered PHB complexes and abolishes mitochondrial tubular networks. We found that PHB2 associated with a caseinolytic peptidase B protein homolog, also known as mitochondrial ATPase associated with diverse cellular activities ATPase chaperonin, via a coiled-coil, thereby ensuring mitochondrial-mediated antiviral innate immunity. Elucidation of the PHB complex structure in mitochondria provides insight into essential PHB interactomes required for mitochondrial dynamics as well as cellular signal transduction.
Keywords: BioID, crystal structure, homeostasis, innate immunity, interactome, mitochondrial dynamics, prohibitin, RNA virus, scaffolding, signal transduction
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