Structural basis of BAX pore formation

• 成果类型: Article
• 署名作者: Zhang, Ying; Tian, Lu; Huang, Gaoxingyu; Ge, Xiaofei; Kong, Fang; Wang, Pengqi; Xu, Yige; Shi, Yigong
• 署名单位: Tsinghua University; Westlake Laboratory; Westlake University; Westlake University; Westlake University; Tsinghua University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10506
• DOI: 10.1126/science.adv4314
• 发表日期: 2025-06-26
• 关键词: cryo-em; caspase activation; proapoptotic bax; outer-membrane; cytochrome-c; mitochondria; protein; apoptosis; reveal; form

摘要

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 alpha 9 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.