Molecular basis for pore blockade of human Na + channel Na v 1.2 by the μ-conotoxin KIIIA

Autor: Nieng Yan, Huaizong Shen, Xiaojing Pan, Jianlin Lei, Zhangqiang Li, Gaoxingyu Huang, Shuai Gao, Lei Liu, Xiaoshuang Huang
Rok vydání: 2019
Předmět:
Zdroj: Science. 363:1309-1313
ISSN: 1095-9203
0036-8075
DOI: 10.1126/science.aaw2999
Popis: Targeting sodium channels Voltage-gated sodium (Na v ) channels have been implicated in cardiac and neurological disorders. There are many subtypes of these channels, making it challenging to develop specific therapeutics. A core α subunit is sufficient for voltage sensing and ion conductance, but function is modulated by β subunits and by natural toxins that can either act as pore blockers or gating modifiers (see the Perspective by Chowdhury and Chanda). Shen et al. present the structures of Na v 1.7 in complex with both β1 and β2 subunits and with animal toxins. Pan et al. present the structure of Na v 1.2 bound to β2 and a toxic peptide, the µ-conotoxin KIIIA. The structure shows why KIIIA is specific for Na v 1.2. These and other recently determined Na v structures provide a framework for targeted drug development. Science , this issue p. 1303 , p. 1309 ; see also p. 1278
Databáze: OpenAIRE
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