An iris diaphragm mechanism to gate a cyclic nucleotide-gated ion channel.

An iris diaphragm mechanism to gate a cyclic nucleotide-gated ion channel.
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虹膜膜片机制,用于栅极循环核苷酸门控离子通道。

DOI:
10.1038/s41467-018-06414-8
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发表时间:
2018-09-28
影响因子:
16.6
通讯作者:
Scheuring S
Scheuring S
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Marchesi A;Gao X;Adaixo R;Rheinberger J;Stahlberg H;Nimigean C;Scheuring S

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环核苷酸门控 (CNG) 离子通道是非选择性阳离子通道,对于信号转导至关重要。环核苷酸(cAMP/cGMP)结合/解除结合的自由能差转化为机械功,以调节孔的打开/关闭概率,即门控。尽管 CNG 通道的结构测定最近取得了进展,但与门控相关的构象变化仍然未知。在这里,我们使用高速原子力显微镜 (HS-AFM) 检查 CNG 通道的原核同源物 SthK 的构象动力学。脂质双层中 SthK 的 HS-AFM 显示 CNBD 在静息(apo 和 cGMP)与激活(cAMP)状态之间的相互转换过程中经历了巨大的构象变化:CNBD 接近膜并远离 4 倍通道轴展开,并伴随着相对于孔域的顺时针旋转。我们建议这些运动可以通过 C-linker 转换,以虹膜隔膜样机制将孔螺旋拉开。环核苷酸门控(CNG)离子通道是信号转导的关键非选择性阳离子通道,但与门控相关的构象变化仍然未知。在这里,作者使用高速原子力显微镜来可视化 SthK 通道对环核苷酸响应的动态。
Cyclic nucleotide-gated (CNG) ion channels are non-selective cation channels key to signal transduction. The free energy difference of cyclic-nucleotide (cAMP/cGMP) binding/unbinding is translated into mechanical work to modulate the open/closed probability of the pore, i.e., gating. Despite the recent advances in structural determination of CNG channels, the conformational changes associated with gating remain unknown. Here we examine the conformational dynamics of a prokaryotic homolog of CNG channels, SthK, using high-speed atomic force microscopy (HS-AFM). HS-AFM of SthK in lipid bilayers shows that the CNBDs undergo dramatic conformational changes during the interconversion between the resting (apo and cGMP) and the activated (cAMP) states: the CNBDs approach the membrane and splay away from the 4-fold channel axis accompanied by a clockwise rotation with respect to the pore domain. We propose that these movements may be converted by the C-linker to pull the pore helices open in an iris diaphragm-like mechanism. Cyclic nucleotide-gated (CNG) ion channels are non-selective cation channels key to signal transduction, but conformational changes associated with gating remained unknown. Here authors use high-speed atomic force microscopy to visualize SthK channels dynamics in response to cyclic nucleotides.
真核环核苷酸门控通道的结构。
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