Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.
Science. 2010 Apr 2;328(5974):67-73. doi: 10.1126/science.1185954.
Voltage sensors regulate the conformations of voltage-dependent ion channels and enzymes. Their nearly switchlike response as a function of membrane voltage comes from the movement of positively charged amino acids, arginine or lysine, across the membrane field. We used mutations with natural and unnatural amino acids, electrophysiological recordings, and x-ray crystallography to identify a charge transfer center in voltage sensors that facilitates this movement. This center consists of a rigid cyclic "cap" and two negatively charged amino acids to interact with a positive charge. Specific mutations induce a preference for lysine relative to arginine. By placing lysine at specific locations, the voltage sensor can be stabilized in different conformations, which enables a dissection of voltage sensor movements and their relation to ion channel opening.
电压传感器调节电压依赖性离子通道和酶的构象。它们作为膜电压函数的近乎开关式响应来自于带正电荷的氨基酸，精氨酸或赖氨酸，穿过膜电场的运动。我们使用具有天然和非天然氨基酸的突变体、电生理记录和 X 射线晶体学来鉴定电压传感器中的电荷转移中心，该中心促进了这种运动。该中心由刚性环状“帽”和两个带负电荷的氨基酸组成，以与正电荷相互作用。特定的突变体诱导相对于精氨酸对赖氨酸的偏好。通过将赖氨酸置于特定位置，电压传感器可以稳定在不同的构象中，从而能够对电压传感器的运动及其与离子通道打开的关系进行剖析。
