National Natural Science Foundation of China (NSFC)
81920108015
中国
National Natural Science Foundation of China (NSFC)
31930059
中国
引用
ジャーナル: Science / 年: 2025 タイトル: Structural basis of BAX pore formation. 著者: Ying Zhang / Lu Tian / Gaoxingyu Huang / Xiaofei Ge / Fang Kong / Pengqi Wang / Yige Xu / Yigong Shi / 要旨: During apoptosis, cytosolic BAX monomers are translocated to the mitochondria to permeabilize the outer membrane. Here, we identified a dimer of BAX dimers as the basic repeating unit of its various ...During apoptosis, cytosolic BAX monomers are translocated to the mitochondria to permeabilize the outer membrane. Here, we identified a dimer of BAX dimers as the basic repeating unit of its various oligomeric forms: arcs, lines, and rings. Cryo-electron microscopy structure of the BAX repeating unit at 3.2-angstrom resolution revealed the interactions within and between dimers. End-to-end stacking of the repeating units through the protruding α9 pairs yielded lines, arcs, polygons, and rings. We structurally characterized the tetragon, pentagon, hexagon, and heptagon, which comprise 16, 20, 24, and 28 BAX protomers, respectively. Missense mutations at the BAX inter-protomer interface damage pore formation and cripple its proapoptotic function. The assembly principle of the various BAX oligomers reported here provides the structural basis of membrane permeabilization by BAX.