Analysis of the structural and molecular basis of voltage-sensitive sodium channel inhibition by the spider toxin huwentoxin-IV (μ-TRTX-Hh2a)

Journal of Biological Chemistry

Volumn 288, Issue 31, 2013, Pages 22707-22720

  Minassian, Natali A ^a   Gibbs, Alan ^a   Shih, Amy Y ^a   Liu, Yi ^a   Neff, Robert A ^a   Sutton, Steven W ^a   Mirzadegan, Tara ^a   Connor, Judith ^a   Fellows, Ross ^a   Husovsky, Matthew ^a   Nelson, Serena ^a   Hunter, Michael J ^a   Flinspach, Mack ^a   Wickenden, Alan D ^a  

^a JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

MOLECULAR BASIS; SODIUM CHANNEL; SPIDER TOXINS; STRUCTURAL FEATURE; STRUCTURE FUNCTIONS; THERAPEUTIC POTENTIALS; TOXIN ACTIVITY; VENOM PEPTIDES;

PEPTIDES;

TOXIC MATERIALS;

ALANINE; ARGININE; ASPARAGINE; ASPARTIC ACID; GLUTAMIC ACID; GLUTAMINE; ISOLEUCINE; LEUCINE; LYSINE; MU HUWENTOXIN HH2A; PHENYLALANINE; PROLINE; RADIOLIGAND; SERINE; SODIUM CHANNEL NAV1.2; SODIUM CHANNEL NAV1.7; SPIDER VENOM; THREONINE; TRYPTOPHAN; TYROSINE; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; ELECTROPHYSIOLOGY; HUMAN; HUMAN CELL; HYDROPHOBICITY; LIGAND BINDING; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MOLECULAR INTERACTION; MOLECULAR MODEL; MUTAGENESIS; NUCLEAR MAGNETIC RESONANCE; PATCH CLAMP; PREDICTION; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FOLDING; STRUCTURE ANALYSIS; TARANTULA; TOXIN ANALYSIS; TOXIN STRUCTURE;

ELECTROPHYSIOLOGY; ION CHANNELS; SODIUM CHANNELS; STRUCTURAL BIOLOGY; TOXINS;

AMINO ACID SEQUENCE; HEK293 CELLS; HUMANS; ION CHANNEL GATING; MAGNETIC RESONANCE SPECTROSCOPY; MOLECULAR DYNAMICS SIMULATION; MOLECULAR SEQUENCE DATA; RADIOLIGAND ASSAY; SEQUENCE HOMOLOGY, AMINO ACID; SODIUM CHANNEL BLOCKERS; SPIDER VENOMS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84881260895     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.461392     Document Type: Article

References (54)

1. King, G. F. (2004) The wonderful world of spiders. Preface to the special Toxicon issue on spider venoms. Toxicon 43, 471-475
2. Escoubas, P. (2006) Molecular diversification in spider venoms. A web of combinatorial peptide libraries. Mol. Divers. 10, 545-554
3. Herzig, V., Wood, D. L., Newell, F., Chaumeil, P. A., Kaas, Q., Binford, G. J., Nicholson, G. M., Gorse, D., and King, G. F. (2011) ArachnoServer 2.0, an updated online resource for spider toxin sequences and structures. Nucleic Acids Res. 39, D653-D657
4. Wood, D. L., Miljenović, T., Cai, S., Raven, R. J., Kaas, Q., Escoubas, P., Herzig, V., Wilson, D., and King, G. F. (2009) ArachnoServer: a database of protein toxins from spiders. BMC Genomics 10, 375
5. Bosmans, F., Rash, L., Zhu, S., Diochot, S., Lazdunski, M., Escoubas, P., and Tytgat, J. (2006) Four novel tarantula toxins as selective modulators of voltage-gated sodium channel subtypes. Mol. Pharmacol. 69, 419-429
6. King, G. F., Escoubas, P., and Nicholson, G. M. (2008) Peptide toxins that selectively target insect Na(V) and Ca(V) channels. Channels 2, 100-116
7. Middleton, R. E., Warren, V. A., Kraus, R. L., Hwang, J. C., Liu, C. J., Dai, G., Brochu, R. M., Kohler, M. G., Gao, Y. D., Garsky, V. M., Bogusky, M. J., Mehl, J. T., Cohen, C. J., and Smith, M. M. (2002) Two tarantula peptides inhibit activation of multiple sodium channels. Biochemistry 41, 14734-14747
8. Xiao, Y., Bingham, J. P., Zhu, W., Moczydlowski, E., Liang, S., and Cummins, T. R. (2008) Tarantula huwentoxin-IV inhibits neuronal sodium channels by binding to receptor site 4 and trapping the domain ii voltage sensor in the closed configuration. J. Biol. Chem. 283, 27300-27313
9. Xiao, Y., and Liang, S. (2003) Inhibition of neuronal tetrodotoxin-sensitive Na+ channels by two spider toxins. Hainantoxin-III and hainantoxin-IV. Eur. J. Pharmacol. 477, 1-7
10. Yogeeswari, P., Ragavendran, J. V., Thirumurugan, R., Saxena, A., and Sriram, D. (2004) Ion channels as important targets for antiepileptic drug design. Curr. Drug Targets 5, 589-602
11. Noble, D. (2002) Unraveling the genetics and mechanisms of cardiac arrhythmia. Proc. Natl. Acad. Sci. U.S.A. 99, 5755-5756
12. Cannon, S. C. (2000) Spectrum of sodium channel disturbances in the nondystrophic myotonias and periodic paralyses. Kidney Int. 57, 772-779
13. Wood, J. N., Boorman, J. P., Okuse, K., and Baker, M. D. (2004) Voltagegated sodium channels and pain pathways. J. Neurobiol. 61, 55-71
14. Saez, N. J., Senff, S., Jensen, J. E., Er, S. Y., Herzig, V., Rash, L. D., and King, G. F. (2010) Spider-venom peptides as therapeutics. Toxins 2, 2851-2871
15. Klint, J. K., Senff, S., Rupasinghe, D. B., Er, S. Y., Herzig, V., Nicholson, G. M., and King, G. F. (2012) Spider-venom peptides that target voltagegated sodium channels. Pharmacological tools and potential therapeutic leads. Toxicon 60, 478-491
16. Liang, S. P., Zhang, D. Y., Pan, X., Chen, Q., and Zhou, P. A. (1993) Properties and amino acid sequence of huwentoxin-I, a neurotoxin purified from the venom of the Chinese bird spider Selenocosmia huwena. Toxicon 31, 969-978
17. Xiao, Y., Luo, X., Kuang, F., Deng, M., Wang, M., Zeng, X., and Liang, S. (2008) Synthesis and characterization of huwentoxin-IV, a neurotoxin inhibiting central neuronal sodium channels. Toxicon 51, 230-239
18. Xiao, Y., Blumenthal, K., Jackson, J. O., 2nd, Liang, S., and Cummins, T. R. (2010) The tarantula toxins ProTx-II and huwentoxin-IV differentially interact with human Nav1.7 voltage sensors to inhibit channel activation and inactivation. Mol. Pharmacol. 78, 1124-1134
19. Xiao, Y., Jackson, J. O., 2nd, Liang, S., and Cummins, T. R. (2011)Common molecular determinants of tarantula huwentoxin-IV inhibition of Na+ channel voltage sensors in domains II and IV. J. Biol. Chem. 286, 27301-27310
20. Li, D., Xiao, Y., Xu, X., Xiong, X., Lu, S., Liu, Z., Zhu, Q., Wang, M., Gu, X., and Liang, S. (2004) Structure-activity relationships of hainantoxin-IV and structure determination of active and inactive sodium channel blockers. J. Biol. Chem. 279, 37734-37740
21. Liu, Y., Li, D., Wu, Z., Li, J., Nie, D., Xiang, Y., and Liu, Z. (2012) A positively charged surface patch is important for hainantoxin-IV binding to voltage-gated sodium channels. J. Pept. Sci. 18, 643-649
22. Liu, Y., Beck, E. J., and Flores, C. M. (2011) Validation of a patch clamp screening protocol that simultaneously measures compound activity in multiple states of the voltage-gated sodium channel Nav1.2. Assay Drug Dev. Technol. 9, 628-634
23. Roland, B. L., Sutton, S. W., Wilson, S. J., Luo, L., Pyati, J., Huvar, R., Erlander, M. G., and Lovenberg, T. W. (1999) Anatomical distribution of prolactin-releasing peptide and its receptor suggests additional functions in the central nervous system and periphery. Endocrinology 140, 5736-5745
24. Bax, A., and Davis, D. G. (1985) MLEV-17 based two-dimensional homonuclear magnetization transfer spectroscopy. J. Magn. Reson. 65, 355-360
25. Jeener, J., Meier, B. H. Bachmann, P., Ernst, R. R. (1979) Investigation of exchange processes by two-dimensional NMR spectroscopy. J. Chem. Phys. 71, 4546-4553
26. Cavanagh, J., Fairbrother, W., Palmer, A. G., III, and Skleton, N. J. (2007) Protein NMR Spectroscopy: Principles and Practice, 2nd Ed., Pp. 535-673, Academic Press, Inc., New York
27. Delaglio, F., Grzesiek, S., Vuister, G. W., Zhu, G., Pfeifer, J., Bax, A. (1995) NMRPipe. A multidimensional spectral processing system based on UNIX pipes. J. Biomol. NMR 6, 277-293
28. Güntert, P. (2004) Automated NMR structure calculation with CYANA. Methods Mol. Biol. 278, 353-378
29. Berjanskii, M. V., Neal, S., and Wishart, D. S. (2006) PREDITOR. A web server for predicting protein torsion angle restraints. Nucleic Acids Res. 34, W63-W69
30. Cheung, M. S., Maguire, M. L., Stevens, T. J., and Broadhurst, R. W. (2010) DANGLE. A Bayesian inferential method for predicting protein backbone dihedral angles and secondary structure. J. Magn. Reson. 202, 223-233
31. Phillips, J. C., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., Chipot, C., Skeel, R. D., Kalé, L., and Schulten, K. (2005) Scalable molecular dynamics with NAMD. J. Comput. Chem. 26, 1781-1802
32. Mackerell, A. D., Jr., Feig, M., and Brooks, C. L., 3rd. (2004) Extending the treatment of backbone energetics in protein force fields. Limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations. J. Comput. Chem. 25, 1400-1415
33. Humphrey, W., Dalke, A., and Schulten, K. (1996) VMD. Visual molecular dynamics. J. Mol. Graph. 14, 33-38, 27-28
34. Payandeh, J., Scheuer, T., Zheng, N., and Catterall, W. A. (2011) The crystal structure of a voltage-gated sodium channel. Nature 475, 353-358
35. Khalili-Araghi, F., Jogini, V., Yarov-Yarovoy, V., Tajkhorshid, E., Roux, B., and Schulten, K. (2010) Calculation of the gating charge for the Kv1.2 voltage-activated potassium channel. Biophys. J. 98, 2189-2198
36. Spassov, V. Z., Yan, L., and Szalma, S. (2002) Introducing an implicit membrane in generalized born/solvent accessibility continuum solvent models. J. Phys. Chem. B 106, 8726-8738
37. Peng, K., Shu, Q., Liu, Z., and Liang, S. (2002) Function and solution structure of huwentoxin-IV, a potent neuronal tetrodotoxin (TTX)-sensitive sodium channel antagonist from Chinese bird spider Selenocosmia huwena. J. Biol. Chem. 277, 47564-47571
38. Lee, S., Milescu, M., Jung, H. H., Lee, J. Y., Bae, C. H., Lee, C. W., Kim, H. H., Swartz, K. J., and Kim, J. I. (2010) Solution structure of GxTX-1E, a high-affinity tarantula toxin interacting with voltage sensors in Kv2.1 potassium channels. Biochemistry 49, 5134-5142
39. Takahashi, H., Kim, J. I., Min, H. J., Sato, K., Swartz, K. J., and Shimada, I. (2000) Solution structure of hanatoxin1, a gating modifier of voltage-dependent K+ channels. Common surface features of gating modifier toxins. J. Mol. Biol. 297, 771-780
40. Wang, J. M., Roh, S. H., Kim, S., Lee, C. W., Kim, J. I., and Swartz, K. J. (2004) Molecular surface of tarantula toxins interacting with voltage sensors in Kv channels. J. Gen. Physiol. 123, 455-467
41. Mouhat, S., De Waard, M., and Sabatier, J. M. (2005) Contribution of the functional dyad of animal toxins acting on voltage-gated Kv1-type channels. J. Pept. Sci. 11, 65-68
42. Chagot, B., Escoubas, P., Villegas, E., Bernard, C., Ferrat, G., Corzo, G., Lazdunski, M., and Darbon, H. (2004) Solution structure of phrixotoxin 1, a specific peptide inhibitor of Kv4 potassium channels from the venom of the theraphosid spider Phrixotrichus auratus. Protein Sci. 13, 1197-1208
43. Fiorucci, S., and Zacharias, M. (2010) Prediction of protein-protein interaction sites using electrostatic desolvation profiles. Biophys. J. 98, 1921-1930
44. Burgoyne, N. J., and Jackson, R. M. (2006) Predicting protein interaction sites. Binding hot-spots in protein-protein and protein-ligand interfaces. Bioinformatics 22, 1335-1342
45. Gallivan, J. P., Dougherty, D. A. (2000) A computational study of cation-α interactions vs. salt bridges in aqueous media. Implications for protein engineering. J. Am. Chem. Soc. 122, 870-874
46. Zhang, J. Z., Yarov-Yarovoy, V., Scheuer, T., Karbat, I., Cohen, L., Gordon, D., Gurevitz, M., and Catterall, W. A. (2012) Mapping the interaction site for a γ-scorpion toxin in the pore module of domain III of voltage-gated Na+ channels. J. Biol. Chem. 287, 30719-30728
47. Zhang, J. Z., Yarov-Yarovoy, V., Scheuer, T., Karbat, I., Cohen, L., Gordon, D., Gurevitz, M., and Catterall, W. A. (2011) Structure-function map of the receptor site for-scorpion toxins in domain II of voltage-gated sodium channels. J. Biol. Chem. 286, 33641-33651
48. Yang, Y., Wang, Y., Li, S., Xu, Z., Li, H., Ma, L., Fan, J., Bu, D., Liu, B., Fan, Z., Wu, G., Jin, J., Ding, B., Zhu, X., and Shen, Y. (2004) Mutations in SCN9A, encoding a sodium channelα subunit, in patients with primary erythermalgia. J. Med. Genet. 41, 171-174
49. Fertleman, C. R., Baker, M. D., Parker, K. A., Moffatt, S., Elmslie, F. V., Abrahamsen, B., Ostman, J., Klugbauer, N., Wood, J. N., Gardiner, R. M., and Rees, M. (2006) SCN9A mutations in paroxysmal extreme pain disorder. Allelic variants underlie distinct channel defects and phenotypes. Neuron 52, 767-774
50. Cox, J. J., Reimann, F., Nicholas, A. K., Thornton, G., Roberts, E., Springell, K., Karbani, G., Jafri, H., Mannan, J., Raashid, Y., Al-Gazali, L., Hamamy, H., Valente, E. M., Gorman, S., Williams, R., McHale, D. P., Wood, J. N., Gribble, F. M., and Woods, C. G. (2006) An SCN9A channelopathy causes congenital inability to experience pain. Nature 444, 894-898
51. Goldberg, Y. P., MacFarlane, J., MacDonald, M. L., Thompson, J., Dube, M. P., Mattice, M., Fraser, R., Young, C., Hossain, S., Pape, T., Payne, B., Radomski, C., Donaldson, G., Ives, E., Cox, J., Younghusband, H. B., Green, R., Duff, A., Boltshauser, E., Grinspan, G. A., Dimon, J. H., Sibley, B. G., Andria, G., Toscano, E., Kerdraon, J., Bowsher, D., Pimstone, S. N., Samuels, M. E., Sherrington, R., and Hayden, M. R. (2007) Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations. Clin. Genet. 71, 311-319
52. Ahmad, S., Dahllund, L., Eriksson, A. B., Hellgren, D., Karlsson, U., Lund, P. E., Meijer, I. A., Meury, L., Mills, T., Moody, A., Morinville, A., Morten, J., O'donnell, D., Raynoschek, C., Salter, H., Rouleau, G. A., and Krupp, J. J. (2007) A stop codon mutation in SCN9A causes lack of pain sensation. Hum. Mol. Genet. 16, 2114-2121
53. Meisler, M. H., O'Brien, J. E., and Sharkey, L. M. (2010) Sodium channel gene family. Epilepsy mutations, gene interactions and modifier effects. J. Physiol. 588, 1841-1848
54. Sanders, S. J., Murtha, M. T., Gupta, A. R., Murdoch, J. D., Raubeson, M. J., Willsey, A. J., Ercan-Sencicek, A. G., DiLullo, N. M., Parikshak, N. N., Stein, J. L., Walker, M. F., Ober, G. T., Teran, N. A., Song, Y., El-Fishawy, P., Murtha, R. C., Choi, M., Overton, J. D., Bjornson, R. D., Carriero, N. J., Meyer, K. A., Bilguvar, K., Mane, S. M., Sestan, N., Lifton, R. P., Günel, M., Roeder, K., Geschwind, D. H., Devlin, B., and State, M. W. (2012) De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 485, 237-241