During apoptosis Bcl-2 changes membrane topology at both the endoplasmic reticulum mitochondria
During apoptosis Bcl-2 changes membrane topology at both the endoplasmic reticulum mitochondria
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DOI：
10.1016/s1097-2765(04)00263-1
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发表时间：
2004-05-21
期刊：
影响因子：
16
通讯作者：
Andrews, DW
中科院分区：
文献类型：
--
作者：
Kim, PK;Annis, MG;Andrews, DW
在健康细胞中，抗凋亡蛋白 Bcl-2 采用尾部锚定蛋白的典型拓扑结构，仅将疏水性羧基末端插入膜中，如用不透膜的巯基特异性试剂标记细胞裂解物所示。细胞凋亡的诱导引发了 Bcl-2 构象的变化，使得靠近螺旋 5 基部的半胱氨酸 158 插入内质网和线粒体的脂质双层中，从而免受标记。将与促凋亡蛋白 Bim 的 BH3 结构域相对应的肽添加到细胞裂解物中，会引发 Bcl-2 中类似的构象变化，这表明预先存在的膜结合 Bcl-2 蛋白改变了拓扑结构。
In healthy cells the antiapoptotic protein Bcl-2 adopts a topology typical of tail-anchored proteins with only the hydrophobic carboxyl terminus inserted into the membrane, as shown by labeling cell lysates with a membrane-impermeant sulfhydryl-specific reagent. Induction of apoptosis in cells triggered a change in the conformation of Bcl-2 such that cysteine 158 near the base of helix 5 inserted into the lipid bilayer of both endoplasmic reticulum and mitochondria where it was protected from labeling. Addition of a peptide corresponding to the BH3 domain of the proapoptotic protein Bim to cell lysates triggered a similar conformational change in Bcl-2, demonstrating that preexisting, membrane-bound Bcl-2 proteins change topology.