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PMID:11055992
| Citation |
Winterfield, JR and Swartz, KJ (2000) A hot spot for the interaction of gating modifier toxins with voltage-dependent ion channels. J. Gen. Physiol. 116:637-44 |
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| 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. |
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| Keywords |
Animals; Binding Sites; Brain/physiology; Calcium Channel Blockers/pharmacology; Calcium Channels/drug effects; Calcium Channels/physiology; DNA, Complementary/genetics; Glutamine/metabolism; Ion Channel Gating/drug effects; Ion Channel Gating/physiology; Muscle, Skeletal/physiology; Mutagenesis, Site-Directed; Point Mutation; Rabbits; Rats; Spider Venoms/pharmacology; omega-Agatoxin IVA/pharmacology |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0019855: calcium channel inhibitor activity |
ECO:0000314: |
F |
Fig. 2 |
complete | ||||
See also
References
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