Mapping the receptor site for ergtoxin, a specific blocker of ERG channels.
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.
Pardo-López
Liliana
L
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.
García-Valdés
Jesús
J
Gurrola
Georgina B
GB
Robertson
Gail A
GA
Possani
Lourival D
LD
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D027682:Cation Transport Proteins; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D004594:Electrophysiology; D051638:Ether-A-Go-Go Potassium Channels; D005260:Female; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes; D026902:Potassium Channel Blockers / Q000378:metabolism* / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012604:Scorpion Venoms / Q000378:metabolism* / Q000494:pharmacology; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014982:Xenopus laevis
D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; C496885:Kcnh1 protein, mouse; C000606915:Kcnh2 protein, mouse; D008024:Ligands; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011993:Recombinant Fusion Proteins; D012604:Scorpion Venoms; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; C118951:ergotoxin, Centruroides noxius