Positions of the cytoplasmic end of BK α S0 helix relative to S1-S6 and of β1 TM1 and TM2 relative to S0-S6.
Positions of the cytoplasmic end of BK α S0 helix relative to S1-S6 and of β1 TM1 and TM2 relative to S0-S6.
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DOI：
10.1085/jgp.201411337
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发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
Karlin A
中科院分区：
文献类型：
--
作者：
Liu G;Zakharov SI;Yao Y;Marx SO;Karlin A
BK β1亚基置换BK α胞内侧而非胞外侧的独特S 0跨膜螺旋，从而改变其通过膜的路径。大电导、电压门控和钙门控K+（BK）通道由四个α亚基和多达四个调节性β亚基组成，α亚基形成电压门控和钙门控通道。β1亚基在平滑肌中表达，在[Ca 2 +] > 2 µM时，它减慢BK通道动力学并使电导-电压（G-V）曲线左移。除了在所有电压依赖性K+通道中保守的六个跨膜（TM）螺旋S1-S6外，BK α还有一个独特的第七个TM螺旋S 0，这可能导致BK α在β1不存在时G-V曲线发生异常的α-位移，而在β 1存在时发生α-位移。这样的作用是支持的S 0到S3和S4在电压敏感域中的紧密接近。此外，在膜的细胞外侧，β1的两个TM螺旋之一TM 2与S 0相邻。我们现在已经分析了膜的细胞质侧上的取代的Cys残基之间的诱导二硫键形成。相反，在那里，S 0最接近S2-S3环，在加入β1时，它从该位置移位。β1 TM 1和TM 2的胞质末端相邻，位于一个α亚基的S2-S3环和相邻α亚基的S1之间，不与S 0相邻;即，S 0和TM 2具有不同的穿过膜的轨迹。在不存在β1的情况下，W 43 C（S 0）和L175 C（S2-S3）的70%的二硫键对V50的活化没有影响，这意味着S 0的胞质末端和S2-S3环在活化期间一致移动（如果有的话）。否则，在一个状态中将它们连接在一起会阻碍到另一个状态的过渡，这肯定会改变V50。
The BK β1 subunit displaces the unique S0 transmembrane helix on the intracellular side of BK α but not on the extracellular side, thereby altering its path through the membrane. The large-conductance, voltage- and Ca2+-gated K+ (BK) channel consists of four α subunits, which form a voltage- and Ca2+-gated channel, and up to four modulatory β subunits. The β1 subunit is expressed in smooth muscle, where it slows BK channel kinetics and shifts the conductance–voltage (G-V) curve to the left at [Ca2+] > 2 µM. In addition to the six transmembrane (TM) helices, S1–S6, conserved in all voltage-dependent K+ channels, BK α has a unique seventh TM helix, S0, which may contribute to the unusual rightward shift in the G-V curve of BK α in the absence of β1 and to a leftward shift in its presence. Such a role is supported by the close proximity of S0 to S3 and S4 in the voltage-sensing domain. Furthermore, on the extracellular side of the membrane, one of the two TM helices of β1, TM2, is adjacent to S0. We have now analyzed induced disulfide bond formation between substituted Cys residues on the cytoplasmic side of the membrane. There, in contrast, S0 is closest to the S2–S3 loop, from which position it is displaced on the addition of β1. The cytoplasmic ends of β1 TM1 and TM2 are adjacent and are located between the S2–S3 loop of one α subunit and S1 of a neighboring α subunit and are not adjacent to S0; i.e., S0 and TM2 have different trajectories through the membrane. In the absence of β1, 70% of disulfide bonding of W43C (S0) and L175C (S2–S3) has no effect on V50 for activation, implying that the cytoplasmic end of S0 and the S2–S3 loop move in concert, if at all, during activation. Otherwise, linking them together in one state would obstruct the transition to the other state, which would certainly change V50.
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影响因子：
64.8
作者：
Long, Stephen B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1073/pnas.96.7.4137
发表时间：
1999-03-30
影响因子：
11.1
作者：
Wallner, M;Meera, P;Toro, L
通讯作者：
Toro, L
DOI：
10.1016/s0006-291x(74)80213-5
发表时间：
1974-01-01
影响因子：
3.1
作者：
KOSOWER, EM;KOSOWER, NS;LEVY, L
通讯作者：
LEVY, L
影响因子：
4.8
作者：
Brenner, R;Jegla, TJ;Aldrich, RW
通讯作者：
Aldrich, RW