Mapping the receptor site for ergtoxin, a specific blocker of ERG channels

FEBS Letters

Possani, Lourival D.¹  Garcı́a-Valdés, Jesús¹  Pardo-López, Liliana¹  Robertson, Gail A.²  Gurrola, Georgina B.¹ 

[1] Department of Molecular Recognition and Structural Biology, Institute of Biotechnology, National Autonomous University of Mexico, Avenida Universidad 2001, P.O. Box 510-3, Cuernavaca 62210, Mexico;Department of Physiology, Wisconsin University, Madison Medical School, Madison, WI 53706, USA

关键词: Human ether-a-go-go-related gene channel;    K+ channel;    Ergtoxin;    M-elk channel;    M-eag channel;    Scorpion toxin;   

DOI  :  10.1016/S0014-5793(01)03218-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We show here that ergtoxin (ErgTx) is a bona fide, specific blocker of the human ether-a-go-go-related gene (HERG) channels. It does not affect the function of either M-eag or M-elk channels. A chimeric construction containing a segment of the P-region of M-eag channel inserted into the HERG channel drastically diminished or completely abolished the inhibitory effect of ErgTx, whereas chimeras of the P-region of HERG channel into M-eag channels recovered the inhibitory effect. From the P-region point mutants of HERG channel assays, only the mutant N598Q shows about 25% decrement of the ErgTx inhibitory effect. ErgTx recognizes the P-region of HERG channels, blocking the channel function with a K _d in the order of 12 nM.

【 授权许可】

Unknown