Acidic pH promotes oligomerization and membrane insertion of the BclXL apoptotic repressor.
Acidic pH promotes oligomerization and membrane insertion of the BclXL apoptotic repressor.
复制标题
酸性 pH 值可促进 BclXL 凋亡抑制蛋白的寡聚化和膜插入。
DOI：
10.1016/j.abb.2012.08.009
复制
发表时间：
2012
影响因子：
3.9
通讯作者：
Farooq,Amjad
中科院分区：
文献类型：
--
作者：
Bhat,Vikas;Kurouski,Dmitry;Olenick,MaxB;McDonald,CalebB;Mikles,DavidC;Deegan,BrianJ;Seldeen,KennethL;Lednev,IgorK;Farooq,Amjad
Solution pH is believed to serve as an intricate regulatory switch in the induction of apoptosis central to embryonic development and cellular homeostasis. Herein, using an array of biophysical techniques, we provide evidence that acidic pH promotes the assembly of BclXL apoptotic repressor into a megadalton oligomer with a plume-like appearance and harboring structural features characteristic of a molten globule. Strikingly, our data reveal that pH tightly modulates not only oligomerization but also ligand binding and membrane insertion of BclXL in a highly subtle manner. Thus, while oligomerization and the accompanying molten globular content of BclXL is least favorable at pH 6, both of these structural features become more pronounced under acidic and alkaline conditions. However, membrane insertion of BclXL appears to be predominantly favored under acidic conditions. In a remarkable contrast, while ligand binding to BclXL optimally occurs at pH 6, it is diminished by an order of magnitude at lower and higher pH. This reciprocal relationship between BclXL oligomerization and ligand binding lends new insights into how pH modulates functional versatility of a key apoptotic regulator and strongly argues that the molten globule may serve as an intermediate primed for membrane insertion in response to apoptotic cues.
