Home LiteratureArticle Details
PMID: 9671721 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 15 ·1998-07-21 ·Pages 8585-9

Li-Smerin Y, Swartz KJ

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.

MeSH Terms
Amino Acid Sequence Animals Calcium Channels/chemistry,drug effects Ion Channel Gating Molecular Sequence Data Peptides/chemistry,pharmacology Peptides, Cyclic/chemistry,pharmacology Potassium Channels/chemistry,drug effects Sequence Homology, Amino Acid Xenopus laevis
Chemicals
Calcium Channels Peptides Peptides, Cyclic Potassium Channels hanatoxin omega-grammotoxin SIA
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Li-Smerin Y
Molecular Physiology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Swartz K J
References (38)
38 references, click to expand
  1. Modification of sodium channel gating in frog myelinated nerve fibres by Centruroides sculpturatus scorpion venom.
    J Physiol. 1975 Jan;244(2):511-34 PMID: 1079869
  2. Voltage-dependent inhibition of N- and P-type calcium channels by the peptide toxin omega-grammotoxin-SIA.
    Mol Pharmacol. 1997 Dec;52(6):1095-104 PMID: 9415720
  3. Sea anemone toxin and scorpion toxin share a common receptor site associated with the action potential sodium ionophore.
    J Biol Chem. 1978 Oct 25;253(20):7393-6 PMID: 29897
  4. Binding of scorpion toxin to receptor sites associated with sodium channels in frog muscle. Correlation of voltage-dependent binding with activation.
    J Gen Physiol. 1979 Sep;74(3):375-91 PMID: 479827
  5. Kinetic analysis of the action of Leiurus scorpion alpha-toxin on ionic currents in myelinated nerve.
    J Gen Physiol. 1985 Nov;86(5):739-62 PMID: 2415671
  6. Gating of Na channels. Inactivation modifiers discriminate among models.
    J Gen Physiol. 1987 Feb;89(2):253-74 PMID: 2435840
  7. Mechanism of charybdotoxin block of the high-conductance, Ca2+-activated K+ channel.
    J Gen Physiol. 1988 Mar;91(3):335-49 PMID: 2454283
  8. Sequence and expression of mRNAs encoding the alpha 1 and alpha 2 subunits of a DHP-sensitive calcium channel.
    Science. 1988 Sep 23;241(4873):1661-4 PMID: 2458626
  9. A novel potassium channel with delayed rectifier properties isolated from rat brain by expression cloning.
    Nature. 1989 Aug 24;340(6235):642-5 PMID: 2770868
  10. Mutant potassium channels with altered binding of charybdotoxin, a pore-blocking peptide inhibitor.
    Science. 1989 Sep 22;245(4924):1382-5 PMID: 2476850
  11. Analysis of the blocking activity of charybdotoxin homologs and iodinated derivatives against Ca2+-activated K+ channels.
    J Membr Biol. 1989 Aug;109(3):269-81 PMID: 2477548
  12. Competition for block of a Ca2(+)-activated K+ channel by charybdotoxin and tetraethylammonium.
    Neuron. 1988 Dec;1(10):1003-6 PMID: 2483092
  13. A rat brain Na+ channel alpha subunit with novel gating properties.
    Neuron. 1988 Aug;1(6):449-61 PMID: 2856097
  14. Primary structure and functional expression from complementary DNA of a brain calcium channel.
    Nature. 1991 Apr 4;350(6317):398-402 PMID: 1849233
  15. Identification of amino acid residues involved in dendrotoxin block of rat voltage-dependent potassium channels.
    Mol Pharmacol. 1991 Oct;40(4):572-6 PMID: 1921987
  16. Cloning and tissue-specific expression of the brain calcium channel beta-subunit.
    FEBS Lett. 1991 Oct 21;291(2):253-8 PMID: 1657644
  17. Heterologous regulation of the cardiac Ca2+ channel alpha 1 subunit by skeletal muscle beta and gamma subunits. Implications for the structure of cardiac L-type Ca2+ channels.
    J Biol Chem. 1991 Nov 15;266(32):21943-7 PMID: 1718988
  18. Swapping of functional domains in voltage-gated K+ channels.
    Proc Biol Sci. 1991 Aug 22;245(1313):101-7 PMID: 1682932
  19. Interaction of charybdotoxin with permeant ions inside the pore of a K+ channel.
    Neuron. 1992 Aug;9(2):307-13 PMID: 1379820
  20. Influence of protein surface charge on the bimolecular kinetics of a potassium channel peptide inhibitor.
    Biochemistry. 1993 Jul 13;32(27):6982-7 PMID: 7687466
  21. Isolation and pharmacological characterization of omega-grammotoxin SIA, a novel peptide inhibitor of neuronal voltage-sensitive calcium channel responses.
    Mol Pharmacol. 1993 Aug;44(2):451-60 PMID: 8394998
  22. Electrostatic interactions of S4 voltage sensor in Shaker K+ channel.
    Neuron. 1995 Jun;14(6):1293-301 PMID: 7605638
  23. The charybdotoxin family of K+ channel-blocking peptides.
    Neuron. 1995 Jul;15(1):5-10 PMID: 7542463
  24. An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula.
    Neuron. 1995 Oct;15(4):941-9 PMID: 7576642
  25. Modification of inactivation in cardiac sodium channels: ionic current studies with Anthopleurin-A toxin.
    J Gen Physiol. 1995 Oct;106(4):601-16 PMID: 8576699
  26. Direct physical measure of conformational rearrangement underlying potassium channel gating.
    Science. 1996 Jan 12;271(5246):213-6 PMID: 8539623
  27. Molecular basis of charge movement in voltage-gated sodium channels.
    Neuron. 1996 Jan;16(1):113-22 PMID: 8562074
  28. Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel.
    Neuron. 1996 Jun;16(6):1159-67 PMID: 8663992
  29. Contribution of the S4 segment to gating charge in the Shaker K+ channel.
    Neuron. 1996 Jun;16(6):1169-77 PMID: 8663993
  30. Molecular determinants of high affinity binding of alpha-scorpion toxin and sea anemone toxin in the S3-S4 extracellular loop in domain IV of the Na+ channel alpha subunit.
    J Biol Chem. 1996 Jul 5;271(27):15950-62 PMID: 8663157
  31. Transmembrane movement of the shaker K+ channel S4.
    Neuron. 1996 Feb;16(2):387-97 PMID: 8789953
  32. Measurement of the movement of the S4 segment during the activation of a voltage-gated potassium channel.
    Pflugers Arch. 1996 Nov-Dec;433(1-2):91-7 PMID: 9019737
  33. Alteration of P-type calcium channel gating by the spider toxin omega-Aga-IVA.
    Biophys J. 1997 May;72(5):2117-28 PMID: 9129813
  34. Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites.
    Neuron. 1997 Apr;18(4):665-73 PMID: 9136774
  35. Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K+ channels.
    Neuron. 1997 Apr;18(4):675-82 PMID: 9136775
  36. Purification, characterization, and synthesis of an inward-rectifier K+ channel inhibitor from scorpion venom.
    Biochemistry. 1997 Jun 10;36(23):6936-40 PMID: 9188688
  37. Characterizing voltage-dependent conformational changes in the Shaker K+ channel with fluorescence.
    Neuron. 1997 Nov;19(5):1127-40 PMID: 9390525
  38. Membrane potential-dependent binding of scorpion toxin to the action potential Na+ ionophore. Studies with a toxin derivative prepared by lactoperoxidase-catalyzed iodination.
    J Biol Chem. 1977 Dec 10;252(23):8660-8 PMID: 72754
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.15.8585
Published
1998-07-21
Pages
8585-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC21119
Subset
IM
Grants
NIGMS NIH HHS · R01 GM043949 · United States
Intramural NIH HHS · ZIA NS002945-13 · United States
NIGMS NIH HHS · GM43949 · United States
External Links
PubMed source DOI: 10.1073/pnas.95.15.8585 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2