A Hot Spot for the Interaction of Gating Modifier Toxins with Voltage-Dependent Ion Channels

Content Provider	Semantic Scholar
Author	Winterfield, Jeffrey R. Swartz, Kenton Jon
Copyright Year	2000
Abstract	The gating modifier toxins are a large family of protein toxins that modify either activation or inactivation of voltage-gated ion channels. omega-Aga-IVA is a gating modifier toxin from spider venom that inhibits voltage-gated Ca(2+) channels by shifting activation to more depolarized voltages. We identified two Glu residues near the COOH-terminal edge of S3 in the alpha(1A) Ca(2+) channel (one in repeat I and the other in repeat IV) that align with Glu residues previously implicated in forming the binding sites for gating modifier toxins on K(+) and Na(+) channels. We found that mutation of the Glu residue in repeat I of the Ca(2+) channel had no significant effect on inhibition by omega-Aga-IVA, whereas the equivalent mutation of the Glu in repeat IV disrupted inhibition by the toxin. These results suggest that the COOH-terminal end of S3 within repeat IV contributes to forming a receptor for omega-Aga-IVA. The strong predictive value of previous mapping studies for K(+) and Na(+) channel toxins argues for a conserved binding motif for gating modifier toxins within the voltage-sensing domains of voltage-gated ion channels.
Starting Page	637
Ending Page	644
Page Count	8
File Format	PDF HTM / HTML
PubMed reference number	11055992
Volume Number	116
Journal	The Journal of general physiology
Alternate Webpage(s)	http://jgp.rupress.org/content/116/5/637.full.pdf
Language	English
Access Restriction	Open
Subject Keyword	Binding Sites Chemical Modifier Glutamate Glutamic Acid Hippocampus (Brain) Ion Channel Ions Iontophoresis Iva Mutation Protein Domain Spider Venoms Spiders Stage IVA Cervical Carcinoma Toxin omega-Agatoxin IVA omega-Conotoxin GVIA voltage
Content Type	Text
Resource Type	Article