2. Academic Validation
  3. Structural Basis of Mitochondrial Scaffolds by Prohibitin Complexes: Insight into a Role of the Coiled-Coil Region

Structural Basis of Mitochondrial Scaffolds by Prohibitin Complexes: Insight into a Role of the Coiled-Coil Region

  • iScience. 2019 Sep 27;19:1065-1078. doi: 10.1016/j.isci.2019.08.056.
Takahiro Yoshinaka 1,  Hidetaka Kosako 2,  Takuma Yoshizumi 1,  Ryo Furukawa 1,  Yu Hirano 3,  Osamu Kuge 4,  Taro Tamada 3,  Takumi Koshiba 5
Affiliations

Affiliations

  • 1 Department of Biology, Faculty of Science, Kyushu University, Fukuoka 819-0395, Japan.
  • 2 Division of Cell Signaling, Fujii Memorial Institute of Medical Sciences, Tokushima University, Tokushima 770-8503, Japan.
  • 3 Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology, Ibaraki 319-1106, Japan.
  • 4 Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka 819-0395, Japan.
  • 5 Department of Biology, Faculty of Science, Kyushu University, Fukuoka 819-0395, Japan; Department of Chemistry, Faculty of Science, Fukuoka University, Fukuoka 814-0180, Japan. Electronic address: koshiba@kyudai.jp.
PMID: 31522117 DOI: 10.1016/j.isci.2019.08.056
Abstract

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, showing that 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 abolishes well-ordered PHB complexes and the mitochondrial tubular networks accompanying PHB-dependent signaling. Using a proximity-dependent biotin identification (BioID) technique in live cells, we mapped a number of mitochondrial intermembrane space proteins whose association with PHB2 relies on the HR coiled-coil region. Elucidation of the PHB complex structure in mitochondria provides insight into essential PHB interactomes required for mitochondrial dynamics as well as signal transduction.

Keywords

Cell Biology; Molecular Biology; Structural Biology.

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