Control of a final gating charge transition by a hydrophobic residue in the S2 segment of a K+ channel voltage sensor
Control of a final gating charge transition by a hydrophobic residue in the S2 segment of a K+ channel voltage sensor
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DOI：
10.1073/pnas.1103397108
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发表时间：
2011-04-19
影响因子：
11.1
通讯作者：
Bezanilla, Francisco
中科院分区：
文献类型：
--
作者：
Lacroix, Jerome J.;Bezanilla, Francisco
现在已经确定，电压门控离子通道和一些磷酸酶中存在的电压传感器结构域通过转移几个带电残基（门控电荷），主要是位于S4段的精氨酸，跨越电场进行操作。位于Shaker K通道的S2区段中的保守的苯丙氨酸F-290是芳香族残基，其被认为与S4区段携带的所有四种门控氨基酸相互作用并控制它们的转移[Tao X，et al.（2010）Science 328：67-73]。在本文中，我们研究了可能的相互作用的门控电荷与这个残基直接检测其运动与门控电流测量在12个F-290突变体。大多数突变不会显著改变前约80-90%的门控电荷转移，也不会显著改变激活期间门控电流的动力学。F-290突变体的作用是（i）与ILT突变体的作用类似的占总电荷的约10-20%的最终活化转变的改变[Ledwell JL等人（1999）J Gen Physiol 113：389-414]和（ii）失活期间门控电荷运动的动力学的改变。这些效应与取代残基的疏水性密切相关，表明290位的疏水残基控制了最终门控跃迁的能垒。我们的研究结果表明，F-290控制R-371，第四门控电荷，在门控过程中，而不影响其他三个门控电荷的运动。
It is now well established that the voltage-sensor domains present in voltage-gated ion channels and some phosphatases operate by transferring several charged residues (gating charges), mainly arginines located in the S4 segment, across the electric field. The conserved phenylalanine F-290 located in the S2 segment of the Shaker K channel is an aromatic residue thought to interact with all the four gating arginines carried by the S4 segment and control their transfer [Tao X, et al. (2010) Science 328: 67-73]. In this paper we study the possible interaction of the gating charges with this residue by directly detecting their movement with gating current measurements in 12 F-290 mutants. Most mutations do not significantly alter the first approximately 80-90% of the gating charge transfer nor the kinetics of the gating currents during activation. The effects of the F-290 mutants are (i) the modification of a final activation transition accounting for approximately 10-20% of the total charge, similar to the effect of the ILT mutant [Ledwell JL, et al. (1999) J Gen Physiol 113: 389-414] and (ii) the modification of the kinetics of the gating charge movement during deactivation. These effects are well correlated with the hydrophobicity of the substituted residue, showing that a hydrophobic residue at position 290 controls the energy barrier of the final gating transition. Our results suggest that F-290 controls the transfer of R-371, the fourth gating charge, during gating while not affecting the movement of the other three gating arginines.