The N-terminal domain of a K+ channel beta subunit increases the rate of C-type inactivation from the cytoplasmic side of the channel.
The N-terminal domain of a K+ channel beta subunit increases the rate of C-type inactivation from the cytoplasmic side of the channel.
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K 通道 β 亚基的 N 端结构域增加了通道细胞质侧的 C 型失活率。
DOI：
10.1073/pnas.93.26.15119
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发表时间：
1996
影响因子：
11.1
通讯作者：
Rasmusson,RL
中科院分区：
文献类型：
--
作者：
Morales,MJ;Wee,JO;Wang,S;Strauss,HC;Rasmusson,RL
电压门控性K+通道是膜结合的离子传导α亚基和细胞质辅助（β）亚基的复合物。α和β亚基共表达的主要生理效应是增加α亚基的内在失活速率。对于一个β亚基Kvβ1.1，通过N型机制增强失活。第二个β亚基Kvβ1.2已被证明可增加失活，但通过不同的机制。我们发现Kvβ1.2失活的增强程度依赖于α亚基孔口中的氨基酸组成和细胞外K+的浓度。 促进C型失活的实验条件也增强了Kvβ1.2对失活的刺激，表明该β亚基直接刺激C型失活。仅包含Kvβ1.2的非保守N-末端区域与α亚基融合的嵌合构建体的行为与共表达的Kvβ1.2和α亚基相似。这表明Kvβ1.2的N端结构域介导了孔胞质侧C型失活的增加。我们提出了一个模型，即Kvβ1.2的N末端作为一个弱结合的“球”结构域，与α亚基的细胞内前庭相关联，以影响构象变化，从而增强C型失活。
Voltage-gated K+channels are complexes of membrane-bound, ion-conducting α and cytoplasmic ancillary (β) subunits. The primary physiologic effect of coexpression of α and β subunits is to increase the intrinsic rate of inactivation of the α subunit. For one β subunit, Kvβ1.1, inactivation is enhanced through an N-type mechanism. A second β subunit, Kvβ1.2, has been shown to increase inactivation, but through a distinct mechanism. Here we show that the degree of enhancement of Kvβ1.2 inactivation is dependent on the amino acid composition in the pore mouth of the α subunit and the concentration of extracellular K+. Experimental conditions that promote C-type inactivation also enhance the stimulation of inactivation by Kvβ1.2, showing that this β subunit directly stimulates C-type inactivation. Chimeric constructs containing just the nonconserved N-terminal region of Kvβ1.2 fused with an α subunit behave in a similar fashion to coexpressed Kvβ1.2 and α subunit. This shows that it is the N-terminal domain of Kvβ1.2 that mediates the increase in C-type inactivation from the cytoplasmic side of the pore. We propose a model whereby the N terminus of Kvβ1.2 acts as a weakly binding “ball” domain that associates with the intracellular vestibule of the α subunit to effect a conformational change leading to enhancement of C-type inactivation.