A native prokaryotic voltage-dependent calcium channel with a novel selectivity filter sequence
A native prokaryotic voltage-dependent calcium channel with a novel selectivity filter sequence
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DOI：
10.7554/elife.52828
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发表时间：
2020-02-25
期刊：
影响因子：
7.7
通讯作者：
Irie, Katsumasa
中科院分区：
文献类型：
--
作者：
Shimomura, Takushi;Yonekawa, Yoshiki;Irie, Katsumasa
电压依赖性Ca 2+通道（Caves）对于生物体中动作电位与Ca 2+信号传导的偶联是不可或缺的。Cavs的结构类似于电压依赖性Na+通道（Navs）的结构。已知原核生物Navs可以通过选择性过滤器的负电荷突变获得Ca 2+选择性，但天然原核生物Cavs尚未被鉴定。我们报告的第一个本地原核Cav，CavMr，其选择性过滤器含有比人工原核Cavs的带负电荷的残基的数量较少的识别。一个相对的突变体，其选择性过滤器被替换为CavMr表现出高的Ca 2+选择性。突变分析表明，CavMr选择性过滤器的甘氨酸残基是Ca2+选择性的决定因素。该甘氨酸残基在真核Cavs的亚结构域I和III之间是非常保守的。这些发现提供了新的见解，从原核生物到真核生物保守的Ca2+选择性机制。
Voltage-dependent Ca2+ channels (Cavs) are indispensable for coupling action potentials with Ca2+ signaling in living organisms. The structure of Cavs is similar to that of voltage-dependent Na+ channels (Navs). It is known that prokaryotic Navs can obtain Ca2+ selectivity by negative charge mutations of the selectivity filter, but native prokaryotic Cavs had not yet been identified. We report the first identification of a native prokaryotic Cav, CavMr, whose selectivity filter contains a smaller number of negatively charged residues than that of artificial prokaryotic Cavs. A relative mutant whose selectivity filter was replaced with that of CavMr exhibits high Ca2+ selectivity. Mutational analyses revealed that the glycine residue of the CavMr selectivity filter is a determinant for Ca2+ selectivity. This glycine residue is well conserved among subdomains I and III of eukaryotic Cavs. These findings provide new insight into the Ca2+ selectivity mechanism that is conserved from prokaryotes to eukaryotes.