The RCK1 high-affinity Ca2+ sensor confers carbon monoxide sensitivity to Slo1 BK channels
The RCK1 high-affinity Ca2+ sensor confers carbon monoxide sensitivity to Slo1 BK channels
复制标题
DOI：
10.1073/pnas.0800304105
复制
发表时间：
2008-03-11
影响因子：
11.1
通讯作者：
Hoshi, Toshinori
中科院分区：
文献类型：
--
作者：
Hou, Shangwei;Xu, Rong;Hoshi, Toshinori
一氧化碳 (CO) 是一种致命气体，但它也越来越被认为是一种能够调节多种蛋白质的生理信号分子。其中，大电导Ca2+-和电压门控K+（Slo1 BK）通道在血管舒张和神经元放电中发挥重要作用，被认为可以直接受到CO的刺激。然而，CO对Slo1 BK通道刺激作用的分子机制尚未明确阐明。我们在这里报告，在没有 Ca2+ 的情况下，CO 以独立于电压传感器的方式可靠地、重复地激活切除的膜片中的 Slo1 BK 通道。 CO 对 Slo1 BK 通道的刺激作用需要位于细胞质 RCK1 结构域中的天冬氨酸和两个组氨酸残基，并且在已知抑制其他蛋白质中 CO 和血红素之间的常规相互作用的条件下，该作用持续存在。我们提出 CO 作为 Slo1 BK 通道的 RCK1 结构域中高亲和力二价阳离子传感器的部分激动剂。
Carbon monoxide (CO) is a lethal gas, but it is also increasingly recognized as a physiological signaling molecule capable of regulating a variety of proteins. Among them, large-conductance Ca2+- and voltage-gated K+ (Slo1 BK) channels, important in vasodilation and neuronal firing, have been suggested to be directly stimulated by CO. However, the molecular mechanism of the stimulatory action of CO on the Slo1 BK channel has not been clearly elucidated. We report here that CO reliably and repeatedly activates Slo1 BK channels in excised membrane patches in the absence of Ca2+ in a voltage-sensor-independent manner. The stimulatory action of CO on the Slo1 BK channel requires an aspartic acid and two histidine residues located in the cytoplasmic RCK1 domain, and the effect persists under the conditions known to inhibit the conventional interaction between CO and heme in other proteins. We propose that CO acts as a partial agonist for the high-affinity divalent cation sensor in the RCK1 domain of the Slo1 BK channel.