Lipid-dependent gating of a voltage-gated potassium channel.
Lipid-dependent gating of a voltage-gated potassium channel.
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DOI：
10.1038/ncomms1254
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发表时间：
2011
影响因子：
16.6
通讯作者：
Jiang, Qiu-Xing
中科院分区：
文献类型：
--
作者：
Zheng, Hui;Liu, Weiran;Anderson, Lingyan Y.;Jiang, Qiu-Xing
最近的研究假设，磷脂在激活的构象中稳定了某些电压门控钾通道上的两个电压敏感精氨酸残基。目前尚不清楚血脂是如何直接影响这些通道的。在这里，通过研究KvAP在不同脂类中的构象，我们发现在没有电压变化的情况下，当其周围的脂类从磷脂变为非磷脂时，电压敏感区从激活状态转换到静止状态。这种由脂质决定的构象变化耦合到离子传导孔上，这表明与电压门控平行，通道由其环状脂类门控。我们的测量发现，脂质依赖门控的能量成本接近电压门控，但从动力学上看，它似乎要慢得多。我们的数据支持通道及其周围的脂类共同构成一个功能单位，而天然的非磷脂，如胆固醇，应该对电压门控通道产生强烈的影响。我们对脂类依赖门控的首次观察可能对其他膜蛋白具有普遍意义。脂磷二酯影响某些钾通道的构象，但脂-通道相互作用的细节尚不清楚。这里，当通道从磷脂膜转移到缺乏磷二酯的双层时，发现KvAP通道从激活状态转换到静止状态。
Recent studies hypothesized that phospholipids stabilize two voltage-sensing arginine residues of certain voltage-gated potassium channels in activated conformations. It remains unclear how lipids directly affect these channels. Here, by examining the conformations of the KvAP in different lipids, we showed that without voltage change, the voltage-sensor domains switched from the activated to the resting state when their surrounding lipids were changed from phospholipids to nonphospholipids. Such lipid-determined conformational change was coupled to the ion-conducting pore, suggesting that parallel to voltage gating, the channel is gated by its annular lipids. Our measurements recognized that the energetic cost of lipid-dependent gating approaches that of voltage gating, but kinetically it appears much slower. Our data support that a channel and its surrounding lipids together constitute a functional unit, and natural nonphospholipids such as cholesterol should exert strong effects on voltage-gated channels. Our first observation of lipid-dependent gating may have general implications to other membrane proteins. Lipid phosphodiesters affect the conformation of certain potassium channels, but the details of the lipid-channel interactions are unclear. Here, the KvAP channel is found to switch from an active to a resting state when the channels are transferred from a phospholipid membrane to a bilayer lacking phosphodiesters.
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影响因子：
16.2
作者：
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通讯作者：
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