Importance of lipid–pore loop interface for potassium channel structure and function
Importance of lipid–pore loop interface for potassium channel structure and function
复制标题
DOI：
10.1073/pnas.1305563110
复制
发表时间：
2013-07
期刊：
影响因子：
--
通讯作者：
Elwin A. W. van der Cruijsen;D. Nand;M. Weingarth;A. Prokofyev;Sönke Hornig;A. Cukkemane;A. Bonvin;S. Becker;R. E. Hulse;E. Perozo;O. Pongs;M. Baldus
中科院分区：
文献类型：
--
作者：
Elwin A. W. van der Cruijsen;D. Nand;M. Weingarth;A. Prokofyev;Sönke Hornig;A. Cukkemane;A. Bonvin;S. Becker;R. E. Hulse;E. Perozo;O. Pongs;M. Baldus
钾（即，K+）通道允许钾离子通过保守的孔结构域受控地和选择性地穿过质膜。在电压门控钾离子通道中，门控是两个耦合门协调作用的结果：孔的细胞内入口处的激活门和选择性过滤器处的失活门。通过使用固态NMR结构研究，结合电生理学实验和分子动力学模拟，我们表明，转塔区域连接外跨膜螺旋（跨膜螺旋1）和孔螺旋后面的选择性过滤器有助于K+通道失活，并表现出显着的结构可塑性，与K+通道失活。跨膜螺旋1在K+通道进入失活状态时解旋，并在过渡到闭合状态期间重绕。除了在K+离子配位位点的良好表征的变化之外，该过程还伴随着转塔区域和孔螺旋内的构象变化。进一步的光谱和计算结果表明，相同的通道域是至关重要的孔域和细胞膜之间建立功能性接触。两者合计，我们的研究结果表明，之间的相互作用的K+通道的炮塔区域和脂质双层产生重要的影响，钾离子通过K+通道孔的选择性通过。
Potassium (i.e., K+) channels allow for the controlled and selective passage of potassium ions across the plasma membrane via a conserved pore domain. In voltage-gated K+ channels, gating is the result of the coordinated action of two coupled gates: an activation gate at the intracellular entrance of the pore and an inactivation gate at the selectivity filter. By using solid-state NMR structural studies, in combination with electrophysiological experiments and molecular dynamics simulations, we show that the turret region connecting the outer transmembrane helix (transmembrane helix 1) and the pore helix behind the selectivity filter contributes to K+ channel inactivation and exhibits a remarkable structural plasticity that correlates to K+ channel inactivation. The transmembrane helix 1 unwinds when the K+ channel enters the inactivated state and rewinds during the transition to the closed state. In addition to well-characterized changes at the K+ ion coordination sites, this process is accompanied by conformational changes within the turret region and the pore helix. Further spectroscopic and computational results show that the same channel domain is critically involved in establishing functional contacts between pore domain and the cellular membrane. Taken together, our results suggest that the interaction between the K+ channel turret region and the lipid bilayer exerts an important influence on the selective passage of potassium ions via the K+ channel pore.