Oligomerization of membrane-bound Bcl-2 is involved in its pore formation induced by tBid.
Oligomerization of membrane-bound Bcl-2 is involved in its pore formation induced by tBid.
复制标题
DOI：
10.1007/s10495-009-0389-8
复制
发表时间：
2009-10
期刊：
影响因子：
7.2
通讯作者：
Lin, Jialing
中科院分区：
文献类型：
--
作者：
Peng, Jun;Ding, Jingzhen;Tan, Chibing;Baggenstoss, Bruce;Zhang, Zhi;Lapolla, Suzanne M.;Lin, Jialing
促凋亡Bax和抗凋亡Bcl-2在结构上与细菌毒素的成孔结构域同源。Bax蛋白在线粒体外膜中寡聚化，形成从线粒体膜间隙释放细胞色素c的孔。Bcl-2蛋白也形成孔，然而，比Bax孔小得多。尚不清楚Bcl-2是否形成单体或寡聚体孔。在这里，我们的特点是Bcl-2孔形成脂质体中使用生物物理和生物化学技术。结果表明，随着Bcl-2浓度的增加，Bcl-2孔逐渐增大，表明孔由Bcl-2寡聚体形成。正如从低聚介导的孔形成所预期的，小孔比大孔更早形成。Bcl-2低聚物形成孔的速度比单体，表明低聚构成了孔形成的中间步骤。对寡聚化具有更高亲和力的Bcl-2突变体比野生型Bcl-2更快地形成孔。Bcl-2寡聚体检测条件下，Bcl-2形成孔的脂质体膜中，寡聚化的程度呈正相关的孔形成活性。因此，Bcl-2在形成孔的膜中寡聚化，但寡聚化的程度和所得孔的尺寸比Bax小得多，支持Bcl-2是有缺陷的Bax的模型。
Both proapoptotic Bax and antiapoptotic Bcl-2 are structurally homologous to the pore-forming domain of bacterial toxins. Bax proteins oligomerize in the mitochondrial outer membranes forming pores that release cytochrome c from the mitochondrial intermembrane space. Bcl-2 proteins also form pores that, however, are much smaller than the Bax pore. It is unknown whether Bcl-2 forms monomeric or oligomeric pores. Here, we characterized the Bcl-2 pore formation in liposomes using biophysical and biochemical techniques. The results show that the Bcl-2 pore enlarges as the concentration of Bcl-2 increases, suggesting that the pore is formed by Bcl-2 oligomers. As expected from oligomerization-mediated pore-formation, the small pores are formed earlier than the large ones. Bcl-2 oligomers form pores faster than the monomer, indicating that the oligomerization constitutes an intermediate step of the pore formation. A Bcl-2 mutant with higher affinity for oligomerization forms pores faster than wild type Bcl-2. Bcl-2 oligomers were detected in the liposomal membranes under conditions that Bcl-2 forms pores, and the extent of oligomerization was positively correlated with the pore-forming activity. Therefore, Bcl-2 oligomerizes in membranes forming pores, but the extent of oligomerization and the size of the resulting pores are much smaller than that of Bax, supporting the model that Bcl-2 is a defective Bax.
登录
查看更多内容
影响因子：
11.4
作者：
Dlugosz, Paulina J.;Billen, Lieven P.;Andrews, David W.
通讯作者：
Andrews, David W.
影响因子：
4.8
作者：
Peng, Jun;Tan, Chibing;Lin, Jialing
通讯作者：
Lin, Jialing
DOI：
10.1111/j.1432-1033.1987.tb13655.x
发表时间：
1987-12-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
PAPINI, E;SCHIAVO, G;MONTECUCCO, C
通讯作者：
MONTECUCCO, C
影响因子：
50.3
作者：
Kolluri SK;Zhu X;Zhou X;Lin B;Chen Y;Sun K;Tian X;Town J;Cao X;Lin F;Zhai D;Kitada S;Luciano F;O'Donnell E;Cao Y;He F;Lin J;Reed JC;Satterthwait AC;Zhang XK
通讯作者：
Zhang XK
影响因子：
12.4
作者：
Labi V;Grespi F;Baumgartner F;Villunger A
通讯作者：
Villunger A