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BmP09, a "long chain" scorpion peptide blocker of BK channels
其他题名BmP09,一个长链蝎毒多肽BK钾通道抑制剂
YAO JING; Chen X(陈翔); LI HUI; ZHOU YANG; YAO LIJUN; Wu G(吴宫); CHEN XIAOKE; Zhang NX(张乃霞); ZHOU ZHUAN; XU TAO; Wu HM(吴厚铭); Ding JP(丁久平)
2005
发表期刊J. Biol. Chem.
ISSN0021-9258
卷号280期号:15页码:14819-14828
摘要A novel "long chain" toxin BmP09 has been purified and characterized from the venom of the Chinese scorpion Buthus martensi Karsch. The toxin BmP09 is composed of 66 amino acid residues, including eight cysteines, with a mass of 7721.0 Da. Compared with the B. martensi Karsch AS-1 as a Na+ channel blocker (7704.8 Da), the BmP09 has an exclusive difference in sequence by an oxidative modification at the C terminus. The sulfoxide Met-66 at the C terminus brought the peptide a dramatic switch from a Na+ channel blocker to a K+ channel blocker. Upon probing the targets of the toxin BmP09 on the isolated mouse adrenal medulla chromaffin cells, where a variety of ion channels coexists, we found that the toxin BmP09 specifically blocked large conductance Ca2+- and voltage-dependent K+ channels (BK) but not Na+ channels at a range of 100 nM concentration. This was further confirmed by blocking directly the BK channels encoded with mSlo1 alpha-subunits in Xenopus oocytes. The half-maximum concentration EC50 of BmP09 was 27 nM, and the Hill coefficient was 1.8. In outside-out patches, the 100 nM BmP09 reduced similar to 70% currents of BK channels without affecting the single-channel conductance. In comparison with the "short chain" scorpion peptide toxins such as Charybdotoxin, the toxin BmP09 behaves much better in specificity and reversibility, and thus it will be a more efficient tool for studying BK channels. A three-dimensional simulation between a BmP09 toxin and an mSlo channel shows that the Lys-41 in BmP09 lies at the center of the interface and plugs into the entrance of the channel pore. The stable binding between the toxin BmP09 and the BK channel is favored by aromatic pi-pi interactions around the center.
学科领域生命有机化学
部门归属上海有机所
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收录类别SCI
语种英语
WOS记录号WOS:000228236800060
引用统计
文献类型期刊论文
条目标识符http://ir.sioc.ac.cn/handle/331003/17361
专题上海有机化学研究所
通讯作者Wu HM(吴厚铭); Ding JP(丁久平)
推荐引用方式
GB/T 7714
YAO JING,Chen X,LI HUI,et al. BmP09, a "long chain" scorpion peptide blocker of BK channels[J]. J. Biol. Chem.,2005,280(15):14819-14828.
APA YAO JING.,陈翔.,LI HUI.,ZHOU YANG.,YAO LIJUN.,...&丁久平.(2005).BmP09, a "long chain" scorpion peptide blocker of BK channels.J. Biol. Chem.,280(15),14819-14828.
MLA YAO JING,et al."BmP09, a "long chain" scorpion peptide blocker of BK channels".J. Biol. Chem. 280.15(2005):14819-14828.
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