Contribution of the S4 segment to gating charge in the Shaker K+ channel
Contribution of the S4 segment to gating charge in the Shaker K+ channel
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DOI：
10.1016/s0896-6273(00)80143-9
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发表时间：
1996-06-01
期刊：
影响因子：
16.2
通讯作者：
MacKinnon, R
中科院分区：
文献类型：
--
作者：
Aggarwal, SK;MacKinnon, R
电压激活的离子通道通过将电荷的运动耦合到通道开放来响应膜电压的变化。设计了一种K+通道特异性放射性配体，并用于确定Shaker K+通道中这些门控电荷的来源。Shaker K+通道的打开与13.6个电子电荷单位的位移相关。门控电荷的贡献，确定了六个七个正电荷的S4段，一个不寻常的氨基酸序列在电压激活的阳离子通道组成的重复的基本残基在每三个位置。前四个正电荷的电荷中和突变导致门控电荷大幅减少（类似于每个4个电子电荷单位）;然而，发现Shaker Delta 10的门控电荷与野生型通道相同，Shaker Delta 10是一种在其S4片段中具有10个改变的非碱性残基的Shaker K+通道。这些研究结果表明，运动的NH 2-末端的一半，但不是CO2 H-末端的S4段的门控电荷的基础，这部分的S4段似乎跨越整个跨膜电压差与通道激活。
Voltage-activated ion channels respond to changes in membrane voltage by coupling the movement of charges to channel opening. A K+ channel-specific radioligand was designed and used to determine the origin of these gating charges in the Shaker K+ channel. Opening of a Shaker K+ channel is associated with a displacement of 13.6 electron charge units. Gating charge contributions were determined for six of the seven positive charges in the S4 segment, an unusual amino acid sequence in voltage-activated cation channels consisting of repeating basic residues at every third position. Charge-neutralizing mutations of the first four positive charges led to large decreases (similar to 4 electron charge units each) in the gating charge; however, the gating charge of Shaker Delta 10, a Shaker K+ channel with 10 altered nonbasic residues in its S4 segment, was found to be identical to the wild-type channel. These findings show that movement of the NH2-terminal half but not the CO2H-terminal end of the S4 segment underlies gating charge, and that this portion of the S4 segment appears to move across the entire transmembrane voltage difference in association with channel activation.