IONIC CHANNELS FORMED BY STAPHYLOCOCCUS-AUREUS ALPHA-TOXIN - VOLTAGE-DEPENDENT INHIBITION BY DIVALENT AND TRIVALENT CATIONS
IONIC CHANNELS FORMED BY STAPHYLOCOCCUS-AUREUS ALPHA-TOXIN - VOLTAGE-DEPENDENT INHIBITION BY DIVALENT AND TRIVALENT CATIONS
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DOI：
10.1007/bf01869935
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发表时间：
1986-01-01
影响因子：
2.4
通讯作者：
MENESTRINA, G
中科院分区：
文献类型：
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作者：
MENESTRINA, G
金黄色葡萄球菌α-毒素与平面脂质膜的相互作用导致离子通道的形成，其电导可以在电压钳实验中直接测量。单通道电导率与溶液电导率呈线性关系，表明孔内充满了水溶液；粗略直径为 11.4 .+-。 0.4 .ANG。可以估计毛孔。电导不对称地取决于电压，并且在 pH 7.0 时具有轻微的阴离子选择性，这意味着通道不对称地定向到双层中，并且离子运动至少在孔的一个区域中受到限制。这些孔在 KCl 溶液中通常是开放的，但在二价和三价阳离子存在的情况下会经历剂量和电压依赖性失活，这是由单通道水平的开闭波动介导的。希尔图表明每个通道可以结合两到三个失活阳离子。抑制效率的顺序为 Zn2+ > Tb3+ > Ca2+ > Mg2+ > Ba2+，表明蛋白质的羧基可能参与了结合步骤。提出了一种电压门控失活机制，该机制涉及两种多价阳离子与通道的结合，一种处于开放配置，一种处于封闭配置，并且可以解释失活的电压、剂量和时间依赖性。
The interaction of Staphylococcus aureus .alpha.-toxin with planar lipid membranes results in the formation of ionic channels whose conductance can be directly measured in voltage-clamp experiments. Single-channel conductance depends linearly on the solution conductivity suggesting that the pores are filled with aqueous solution; a rough diameter of 11.4 .+-. 0.4 .ANG. can be estimated for the pore. The conductance depends asymmetrically on voltage and it is slightly anion selective at pH 7.0, which implies that the channels are asymmetrically oriented into the bilayer and that ion motion is restricted at least in a region of the pore. The pores are usually open in a KCl solution but undergo a dose- and voltage-dependent inactivation in the presence of di- and trivalent cations, which is mediated by open-closed fluctuations at the single-channel level. Hill plots indicate that each channel can bind two to three inactivating cations. The inhibiting efficiency follows the sequence Zn2+ > Tb3+ > Ca2+ > Mg2+ > Ba2+, suggesting that carboxyl groups of the protein may be involved in the binding step. A voltage-gated inactivation mechanism is proposed which involves the binding of two polyvalent cations to the channel, one in the open and one in the closed configuration, and which can explain voltage, dose and time dependence of the inactivation.