镁离子介导电压传感器与胞质结构域之间的相互作用以激活大电导钙激活钾通道。
Mg2+ mediates interaction between the voltage sensor and cytosolic domain to activate BK channels.
作者信息
Yang Huanghe, Hu Lei, Shi Jingyi, Delaloye Kelli, Horrigan Frank T, Cui Jianmin
机构信息
Department of Biomedical Engineering and Cardiac Bioelectricity and Arrhythmia Center, Washington University, St. Louis, MO 63130.
出版信息
Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18270-5. doi: 10.1073/pnas.0705873104. Epub 2007 Nov 5.
The voltage-sensor domain (VSD) of voltage-dependent ion channels and enzymes is critical for cellular responses to membrane potential. The VSD can also be regulated by interaction with intracellular proteins and ligands, but how this occurs is poorly understood. Here, we show that the VSD of the BK-type K(+) channel is regulated by a state-dependent interaction with its own tethered cytosolic domain that depends on both intracellular Mg(2+) and the open state of the channel pore. Mg(2+) bound to the cytosolic RCK1 domain enhances VSD activation by electrostatic interaction with Arg-213 in transmembrane segment S4. Our results demonstrate that a cytosolic domain can come close enough to the VSD to regulate its activity electrostatically, thereby elucidating a mechanism of Mg(2+)-dependent activation in BK channels and suggesting a general pathway by which intracellular factors can modulate the function of voltage-dependent proteins.
电压依赖性离子通道和酶的电压传感器结构域（VSD）对于细胞对膜电位的反应至关重要。VSD也可通过与细胞内蛋白质和配体的相互作用进行调节，但具体机制尚不清楚。在这里，我们表明BK型K(+)通道的VSD通过与其自身相连的胞质结构域的状态依赖性相互作用进行调节，这种相互作用依赖于细胞内Mg(2+)和通道孔的开放状态。与胞质RCK1结构域结合的Mg(2+)通过与跨膜片段S4中的Arg-213进行静电相互作用增强VSD激活。我们的结果表明，一个胞质结构域可以与VSD足够接近，从而通过静电作用调节其活性，从而阐明了BK通道中Mg(2+)依赖性激活的机制，并提示了细胞内因子调节电压依赖性蛋白功能的一般途径。
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