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首页> 外文期刊>The Journal of biological chemistry >Pore Helices Play a Dynamic Role as Integrators of Domain Motion during Kv11.1 Channel Inactivation Gating
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Pore Helices Play a Dynamic Role as Integrators of Domain Motion during Kv11.1 Channel Inactivation Gating

机译：孔螺旋在KV11.1通道灭活门控期间发挥为域运动的集成商发挥动态作用

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Proteins that form ion-selective pores in the membrane of cells are integral to many rapid signaling processes, including regulating the rhythm of the heartbeat. In potassium channels, the selectivity filter is critical for both endowing an exquisite selectivity for potassium ions, as well as for controlling the flow of ions through the pore. Subtle rearrangements in the complex hydrogen-bond network that link the selectivity filter to the surrounding pore helices differentiate conducting (open) from nonconducting (inactivated) conformations of the channel. Recent studies suggest that beyond the selectivity filter, inactivation involves widespread rearrangements of the channel protein. Here, we use rate equilibrium free energy relationship analysis to probe the structural changes that occur during selectivity filter gating in Kv11.1 channels, at near atomic resolution. We show that the pore helix plays a crucial dynamic role as a bidirectional interface during selectivity filter gating. We also define the molecular bases of the energetic coupling between the pore helix and outer helix of the pore domain that occurs early in the transition from open to inactivated states, as well as the coupling between the pore helix and inner helix late in the transition. Our data demonstrate that the pore helices are more than just static structural elements supporting the integrity of the selectivity filter; instead they play a crucial dynamic role during selectivity filter gating.
机译：在细胞的膜中形成离子选择性孔的蛋白质是许多快速信号传导过程的一体，包括调节心跳的节奏。在钾通道中，选择性过滤器对于赋予钾离子的精美选择性至关重要，以及通过孔控制离子的流动。在复杂的氢键网络中将选择性滤波器连接到周围的孔螺旋中的微妙重排分化（打开）从通道的非导电（灭活）构象。最近的研究表明，超出选择性过滤器，灭活涉及通道蛋白的广泛重排。这里，我们使用速率平衡能量关系分析来探测在近原子分辨率下在KV11.1通道中选择性滤波器门控过程中发生的结构变化。我们表明，在选择性过滤器门控期间，孔螺旋作为双向界面起到一个关键的动态作用。我们还定义了在从开放到灭活状态的过渡期间发生的孔螺旋和外螺旋之间的能量耦合的分子碱基，以及孔螺旋和在转变中的内部螺旋之间的耦合。我们的数据表明，孔螺旋不仅仅是支持选择性过滤器完整性的静态结构元件;相反，在选择性过滤器门控期间，它们在选择性的动态作用中发挥着重要动态作用。

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