Journal
JOURNAL OF GENERAL PHYSIOLOGY
Volume 116, Issue 5, Pages 637-644Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1085/jgp.116.5.637
Keywords
calcium channels; mutagenesis; agatoxin; voltage-sensing domain
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Funding
- Intramural NIH HHS [ZIA NS002945-13] Funding Source: Medline
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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 Ca2+ channels by shifting activation to more depolarized voltages. We identified two Glu residues near the COOH-terminal edge of S3 in the alpha (1A) Ca2+ channel (one in repeat I and the other in repeat IV) that align with Glu residues previously implicated in for-cling 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 Ca2+ channel had no significant effect on inhibition by omega -Aga-IVA, whereas the equivalent mutation of the Glu in repeat TV disrupted inhibition by the toxin. These results suggest that the COOH-terminal end of 53 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.
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