Structural Basis of Mitochondrial Scaffolds by Prohibitin Complexes: Insight into a Role of the Coiled-Coil Region
| Autor: | Hidetaka Kosako, Yu Hirano, Osamu Kuge, Taro Tamada, Takahiro Yoshinaka, Ryo Furukawa, Takumi Koshiba, Takuma Yoshizumi |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Coiled coil Multidisciplinary Mitochondrial intermembrane space Chemistry 02 engineering and technology Cell Biology macromolecular substances Mitochondrion 021001 nanoscience & nanotechnology Interactome Article Cell biology 03 medical and health sciences Heptad repeat 030104 developmental biology Structural biology Structural Biology lipids (amino acids peptides and proteins) lcsh:Q Prohibitin 0210 nano-technology Inner mitochondrial membrane lcsh:Science Molecular Biology |
| Zdroj: | iScience, Vol 19, Iss, Pp 1065-1078 (2019) iScience |
| ISSN: | 2589-0042 |
| Popis: | Summary 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. Graphical Abstract Highlights • Heptad repeat (HR) region of PHB2 is essential for PHB complexes in mitochondria • The HR region of PHB2 assembles into a dimeric, anti-parallel coiled-coil • Disruption of the PHB2 coiled-coil abolishes mitochondrial dynamics • The coiled-coil associates with mitochondrial proteins, invoking an immune response Molecular Biology; Cell Biology; Structural Biology |
| Databáze: | OpenAIRE |
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