Molecular basis for the toxin insensitivity of scorpion voltage-gated potassium channel MmKv1
Zhang Chuangeng
Xie Zili
Li Xinxin
Chen Jing
Feng Jing
Lang Yange
Yang Weishan
Li Wen-Xin
Chen Zongyun
Yao Jing
Cao Zhijian
Wu Yingliang
· 2016
期刊名称:
Biochemical Journal
2016 年
473 卷
9 期
摘要:
Scorpions are insensitive to their own venoms, which contain various neurotoxins specific for mammalian or insect ion channels, whose molecular mechanism remains unsolved. Using MmKv1, a potassium channel identified from the genome of the scorpion Mesobuthus martensii, channel kinetic experiments showed that MmKv1 was a classical voltage-gated potassium channel with a voltage-dependent fast activation and slow inactivation. Compared with the human Kv1.3 channel (hKv1.3), the MmKv1 channel exhibited a remarkable insensitivity to both scorpion venom and toxin. The chimaeric channels of MmKv1 and hKv1.3 revealed that both turret and filter regions of the MmKv1 channel were critical for the toxin insensitivity of MmKv1. Furthermore, mutagenesis of the chimaeric channel indicated that two basic residues (Arg