Hysteresis of KcsA potassium channel's activation- deactivation gating is caused by structural changes at the channel's selectivity filter.
Hysteresis of KcsA potassium channel's activation- deactivation gating is caused by structural changes at the channel's selectivity filter.
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KcsA 钾通道的激活-失活门控的滞后是由通道选择性滤波器的结构变化引起的。
DOI：
10.1073/pnas.1618101114
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发表时间：
2017
影响因子：
11.1
通讯作者：
Cuello,LuisG
中科院分区：
文献类型：
--
作者：
Tilegenova,Cholpon;Cortes,DMarien;Cuello,LuisG
据报道，离子通道中存在模式漂移或滞后现象。电压门控阳离子通道(VGCC)的门控电流电压漂移被认为是电压敏感域(VSD)的固有特性。然而，将ShakerK+通道的孔域(PD)从VSD中分离出来，阻止了门控电流的模式漂移。因此，有人提出，局部放电的开态稳定会对VSD施加机械载荷，从而导致其模式漂移。此外，超极化门控阳离子通道的模式转换可能是由通道PD的结构变化引起的，类似于潜在的C型失活。为了证明VGCC的局部放电具有滞后性，有必要研究其在没有VSD的情况下的选通过程。一种后门策略是使用KCSA(来自变青链霉菌的K+通道)作为替代品，因为它没有VSD，并且表现出与C型失活耦合的激活。通过直接测量KCSA在促进或阻止C型失活的条件下的激活门的开启和关闭，我们发现：(1)当K+为预指离子时，KCSA经历了门控模式的转变；(2)已知的阻止C-失活的Cs+或Rb+阻止了门控模式的转变；(3)在完全没有C型失活的情况下，KCSA的模式转变被阻止了。最后，我们的结果表明，变构通讯导致KCSA的活化门“记住”选择性过滤器的构象，因此KCSA打开和关闭所需的能量不同。
Mode-shift or hysteresis has been reported in ion channels. Voltage-shift for gating currents is well documented for voltage-gated cation channels (VGCC), and it is considered a voltage-sensing domain's (VSD) intrinsic property. However, uncoupling theShakerK+channel’s pore domain (PD) from the VSD prevented the mode-shift of the gating currents. Consequently, it was proposed that an open-state stabilization of the PD imposes a mechanical load on the VSD, which causes its mode-shift. Furthermore, the mode-shift displayed by hyperpolarization-gated cation channels is likely caused by structural changes at the channel’s PD similar to those underlying C-type inactivation. To demonstrate that the PD of VGCC undergoes hysteresis, it is imperative to study its gating process in the absence of the VSD. A back-door strategy is to use KcsA (a K+channel from the bacteriaStreptomyces lividans) as a surrogate because it lacks a VSD and exhibits an activation coupled to C-type inactivation. By directly measuring KcsA’s activation gate opening and closing in conditions that promote or halt C-type inactivation, we have found (i) that KcsA undergoes mode-shift of gating when having K+as the permeant ion; (ii) that Cs+or Rb+, known to halt C-inactivation, prevented mode-shift of gating; and (iii) that, in the total absence of C-type inactivation, KcsA’s mode-shift was prevented. Finally, our results demonstrate that an allosteric communication causes KcsA's activation gate to “remember” the conformation of the selectivity filter, and hence KcsA requires a different amount of energy for opening than for closing.