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PMID:9671721

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Citation

Li-Smerin, Y and Swartz, KJ (1998) Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels. Proc. Natl. Acad. Sci. U.S.A. 95:8585-9

Abstract

Protein toxins from venomous animals exhibit remarkably specific and selective interactions with a wide variety of ion channels. Hanatoxin and grammotoxin are two related protein toxins found in the venom of the Chilean Rose Tarantula, Phrixotrichus spatulata. Hanatoxin inhibits voltage-gated K+ channels and grammotoxin inhibits voltage-gated Ca2+ channels. Both toxins inhibit their respective channels by interfering with normal operation of the voltage-dependent gating mechanism. The sequence homology of hanatoxin and grammotoxin, as well as their similar mechanism of action, raises the possibility that they interact with the same region of voltage-gated Ca2+ and K+ channels. Here, we show that each toxin can interact with both voltage-gated Ca2+ and K+ channels and modify channel gating. Moreover, mutagenesis of voltage-gated K+ channels suggests that hanatoxin and grammotoxin recognize the same structural motif. We propose that these toxins recognize a voltage-sensing domain or module present in voltage-gated ion channels and that this domain has a highly conserved three-dimensional structure.

Links

PubMed PMC21119

Keywords

Amino Acid Sequence; Animals; Calcium Channels/chemistry; Calcium Channels/drug effects; Ion Channel Gating; Molecular Sequence Data; Peptides/chemistry; Peptides/pharmacology; Peptides, Cyclic/chemistry; Peptides, Cyclic/pharmacology; Potassium Channels/chemistry; Potassium Channels/drug effects; Sequence Homology, Amino Acid; Xenopus laevis

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

GRARO:WGRTX

GO:0019870: potassium channel inhibitor activity

ECO:0000314:

F

Fig. 2

complete
CACAO 4347

GRARO:WGRTX

enables

GO:0019870: potassium channel inhibitor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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