Comparison of the ion channel characteristics of proapoptotic BAX and antiapoptotic BCL-2
Comparison of the ion channel characteristics of proapoptotic BAX and antiapoptotic BCL-2
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DOI：
10.1073/pnas.94.21.11357
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发表时间：
1997-10-14
影响因子：
11.1
通讯作者：
Korsmeyer, SJ
中科院分区：
文献类型：
--
作者：
Schlesinger, PH;Gross, A;Korsmeyer, SJ
BCL-2 蛋白家族由促凋亡和抗凋亡调节因子组成，尽管其最关键的生化功能仍不确定。BCL-X-L 单体与几种离子孔形成细菌毒素之间的结构相似性促进了电生理学研究。 BAX 和 BCL-2 均以 pH 依赖性方式插入 KCl 负载的囊泡中，并表现出宏观离子流出，两种蛋白质的释放在 pH 值约为 4.0 时达到最大；然而，BAX 表现出更广泛的 pH 活性范围，两种纯化蛋白还在 pH 4.0 时插入平面脂质双层中，单通道记录显示 BAX 的最小通道电导为 22 pS，该通道演变成具有至少三个亚电导水平的通道电流。最终，明显稳定的 BAX 通道在 pH 4.0 时的电导为 0.731 nS，当转换到 pH 时，电导变为 0.329 nS 7.0，但仍保持轻度 Cl- 选择性添加主要开放，当 BAX 掺入的脂质囊泡在 pH 7.0 下与平面脂质双层融合时，注意到显示轻度内向整流的 Cl--选择性 (P-K/P-Cl = 0.3) 1.5-nS 通道。相反，BCL-2 形成轻度 K+-选择性 (P-K/P-Cl = 3.9) 通道，其 显着的初始电导为 80 pS，增加至 1.90 nS，在 pH 7.0 下将 BCL-2 掺入的脂质囊泡融合到平面双层中也显示出温和的 K+ 选择性 (P-K/P-Cl = 2.4)，最大电导为 1.08 nS。 BAX和BCL-2各自在人造膜中形成通道，其具有独特的特征，包括离子选择性、电导、电压依赖性和整流。因此，这些分子的作用之一可能包括在选定的膜位点的孔活性。
The BCL-2 family of proteins is composed of both pro-and antiapoptotic regulators, although its most critical biochemical functions remain uncertain, The structural similarity between the BCL-X-L monomer and several ion-pore-forming bacterial toxins has prompted electrophysiologic studies. Both BAX and BCL-2 insert into KCl-loaded vesicles in a pH-dependent fashion and demonstrate macroscopic ion efflux, Release is maximum at approximate to pH 4.0 for both proteins; however, BAX demonstrates a broader pH range of activity, Both purified proteins also insert into planar lipid bilayers at pH 4.0, Single-channel recordings revealed a minimal channel conductance for BAX of 22 pS that evolved to channel currents with at least three subconductance levels, The final, apparently stable BAX channel had a conductance of 0.731 nS at pH 4.0 that changed to 0.329 nS when shifted to pH 7.0 but remained mildly Cl- selective add predominantly open, When BAX-incorporated lipid vesicles were fused to planar lipid bilayers at pH 7.0, a Cl--selective (P-K/P-Cl = 0.3) 1.5-nS channel displaying mild inward rectification was noted, In contrast, BCL-2 formed mildly K+-selective (P-K/P-Cl = 3.9) channels with a most prominent initial conductance of 80 pS that increased to 1.90 nS, Fusion of BCL-2-incorporated lipid vesicles into planar bilayers at pH 7.0 also revealed mild K+ selectivity (P-K/P-Cl = 2.4) with a maximum conductance of 1.08 nS. BAX and BCL-2 each form channels in artificial membranes that have distinct characteristics including ion selectivity, conductance, voltage dependence, and rectification, Thus, one role of these molecules may include pore activity at selected membrane sites.