A residue at the cytoplasmic entrance of BK-type channels regulating single-channel opening by its hydrophobicity.
A residue at the cytoplasmic entrance of BK-type channels regulating single-channel opening by its hydrophobicity.
复制标题
BK 型通道细胞质入口处的残基，通过其疏水性调节单通道开放。
DOI：
10.1529/biophysj.107.120022
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发表时间：
2008-05-01
影响因子：
3.4
通讯作者：
Ding, Jiuping
中科院分区：
文献类型：
--
作者：
Guo, Zhaohua;Lv, Caixia;Yi, Hong;Xiong, Yu;Wu, Yingliang;Li, Wenxin;Xu, Tao;Ding, Jiuping
由mSlo基因编码的单个大电导钙激活K+ (BK)通道通常具有同步门控，但果蝇dSlo （A2/C2/E2/G5/10）剪接变体（dSlo1A）显示非常闪烁的开口。为了探究这种门控的差异，我们构建了一个突变体I323T。该通道具有与dSlo1A相似的四个亚电导电平。当[Ca2+]in从10 μM增加到300 μM时，I323T的单通道电流-电压关系整流减小。诱变表明，该位置残基的疏水性对野生型门控很重要；即疏水性的增加延长了开放时间。分子动力学模拟表明，mSlo 323位的4个疏水孔衬里残基以“类似百叶窗”的机制协同作用，限制K+离子的渗透。速率平衡自由能关系分析表明，mSlo通道中的4个I323残基的构象与门控过程中的闭合构象相似65%。基于这些观察，我们认为bk型通道的整流和基态的出现是由于这四个残基之间的协同性降低和打开的可能性降低所致。
Single large-conductance calcium-activated K+ (BK) channels encoded by the mSlo gene usually have synchronous gating, but a Drosophila dSlo (A2/C2/E2/G5/10) splice variant (dSlo1A) exhibits very flickery openings. To probe this difference in gating, we constructed a mutant I323T. This channel exhibits four subconductance levels similar to those of dSlo1A. Rectification of the single-channel current-voltage relation of I323T decreased as [Ca2+ ]in increased from 10 to 300 μM. Mutagenesis suggests that the hydrophobicity of the residue at the position is important for the wild-type gating; i.e., increasing hydrophobicity prolongs open duration. Molecular dynamics simulation suggests that four hydrophobic pore-lining residues at position 323 of mSlo act cooperatively in a “shutter-like” mechanism gating the permeation of K+ ions. Rate-equilibrium free energy relations analysis shows that the four I323 residues in an mSlo channel have a conformation 65% similar to the closed conformation during gating. Based on these observations, we suggest that the appearance of rectification and substates of BK-type channels arise from a reduction of the cooperativity among these four residues and a lower probability of being open.
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影响因子：
56.9
作者：
NELSON, MT;CHENG, H;LEDERER, WJ
通讯作者：
LEDERER, WJ
DOI：
10.1085/jgp.109.5.647
发表时间：
1997-05
期刊：
The Journal of general physiology
影响因子：
--
作者：
Cui J;Cox DH;Aldrich RW
通讯作者：
Aldrich RW
影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
3.4
作者：
Mitra, A;Tascione, R;Licht, S
通讯作者：
Licht, S
影响因子：
5.7
作者：
Mitra, A;Bailey, TD;Auerbach, AL
通讯作者：
Auerbach, AL