The B-cell lymphoma 2 (BCL2) family members, BCL2-associated protein X (BAX) and BCL2 homologous antagonist killer (BAK), are required for programmed cell death via the mitochondrial pathway. When cells are stressed, damaged or redundant, the balance of power between the BCL2 family of proteins shifts towards BAX and BAK, allowing their transition from an inactive, monomeric state to a membrane-active oligomeric form that releases cytochrome c from the mitochondrial intermembrane space. That oligomeric state has an essential intermediate, a symmetric homodimer of BAX or BAK. Here we describe crystal structures of dimers of the core domain of BAX, comprising its helices α2–α5. These structures provide an atomic resolution description of the interactions that drive BAX homo-dimerisation and insights into potential interaction between core domain dimers and membrane lipids. The previously identified BAK lipid-interacting sites are not conserved with BAX and are likely to determine the differences between them in their interactions with lipids. We also describe structures of heterodimers of BAK/BAX core domains, yielding further insight into the differences in lipid binding between BAX and BAK.

中文翻译：

---

BAX 和 BAK 核心结构域之间的序列差异表现为它们与脂质相互作用的差异

B 细胞淋巴瘤 2 (BCL2) 家族成员、BCL2 相关蛋白 X (BAX) 和 BCL2 同源拮抗剂杀伤剂 (BAK) 是通过线粒体途径进行程序性细胞死亡所必需的。当细胞受到压力、受损或冗余时，BCL2 蛋白家族之间的力量平衡会向 BAX 和 BAK 方向移动，从而使它们从无活性的单体状态转变为膜活性寡聚形式，从而从线粒体膜间隙释放细胞色素c。该寡聚状态有一个重要的中间体，即 BAX 或 BAK 的对称同二聚体。在这里，我们描述了 BAX 核心结构域二聚体的晶体结构，包括其螺旋 α2-α5。这些结构提供了驱动 BAX 同二聚化相互作用的原子分辨率描述，并深入了解了核心域二聚体和膜脂之间的潜在相互作用。先前确定的 BAK 脂质相互作用位点与 BAX 不保守，并且可能决定它们在与脂质相互作用方面的差异。我们还描述了 BAK/BAX 核心域异二聚体的结构，进一步了解 BAX 和 BAK 之间脂质结合的差异。