C-type inactivation underlies important roles played by voltage-gated K⁺ (Kv) channels. Functional studies have provided strong evidence that a common underlying cause of this type of inactivation is an alteration near the extracellular end of the channel's ion-selectivity filter. Unlike N-type inactivation, which is known to reflect occlusion of the channel's intracellular end, the structural mechanism of C-type inactivation remains controversial and may have many detailed variations. Here we report that in voltage-gated Shaker K⁺ channels lacking N-type inactivation, a mutation enhancing inactivation disrupts the outermost K⁺ site in the selectivity filter. Furthermore, in a crystal structure of the Kv1.2-2.1 chimeric channel bearing the same mutation, the outermost K⁺ site, which is formed by eight carbonyl-oxygen atoms, appears to be slightly too small to readily accommodate a K⁺ ion and in fact exhibits little ion density; this structural finding is consistent with the functional hallmark of C-type inactivation.

中文翻译：

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灭活的突变型哺乳动物电压门控K +通道的晶体结构

C型灭活是电压门控K ⁺（Kv）通道发挥重要作用的基础。功能研究提供了有力的证据，表明这种失活的常见根本原因是通道离子选择性过滤器细胞外末端附近的改变。与已知反映通道的细胞内末端闭塞的N型失活不同，C型失活的结构机制仍存在争议，可能会有许多详细的变化。在这里，我们报道在缺乏N型失活的电压门控振荡器K ⁺通道中，增强突变的失活会破坏最外层的K ⁺选择性过滤器中的位置。此外，在带有相同突变的Kv1.2-2.1嵌合通道的晶体结构中，由八个羰基-氧原子形成的最外面的K ⁺位点似乎太小而不能轻易容纳K ⁺离子。实际上几乎没有离子密度；这种结构上的发现与C型失活的功能特点相一致。