BmP09, a "long chain" scorpion peptide blocker of BK channels

CORC > 上海神经科学研究所 > 中国科学院上海生命科学研究院神经科学研究所 > 神经所(总)

	BmP09, a "long chain" scorpion peptide blocker of BK channels
	Yao, J ; Chen, X ; Li, H ; Zhou, Y ; Yao, LJ ; Wu, G ; Chen, X ; Zhang, NX ; Zhou, Z ; Xu, T ; Wu, HM ; Ding, JP
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2005
卷号	280 期号:15 页码:14819-14828
关键词	BUTHUS-MARTENSI KARSCH ADRENAL CHROMAFFIN CELLS DEPENDENT POTASSIUM CHANNELS K+-CHANNELS MOLECULAR-BASIS BMK AS-1 CALCIUM VOLTAGE TOXINS INACTIVATION
ISSN号	0021-9258
通讯作者	Wu, HM (reprint author), Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Bioorgan & Nat Prod Chem, 345 Lingling Lu, Shanghai 200032, Peoples R China,hmwu@mail.sioc.ac.cn ; jpding@mail.hust.edu.cn
英文摘要	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 Ca(2+)- 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 EC(50) 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.
学科主题	Biochemistry & Molecular Biology
收录类别	SCI
语种	英语
公开日期	2012-07-23
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1909]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Yao, J,Chen, X,Li, H,et al. BmP09, a "long chain" scorpion peptide blocker of BK channels[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2005,280(15):14819-14828.
APA	Yao, J.,Chen, X.,Li, H.,Zhou, Y.,Yao, LJ.,...&Ding, JP.(2005).BmP09, a "long chain" scorpion peptide blocker of BK channels.JOURNAL OF BIOLOGICAL CHEMISTRY,280(15),14819-14828.
MLA	Yao, J,et al."BmP09, a "long chain" scorpion peptide blocker of BK channels".JOURNAL OF BIOLOGICAL CHEMISTRY 280.15(2005):14819-14828.