Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 245K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JGP Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Winterfield, J. R. Articles by Swartz, K. J. Search for Related Content PubMed PubMed Citation Articles by Winterfield, J. R. Articles by Swartz, K. J. Social Bookmarking                            What's this?

Original Article

^a Molecular Physiology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892
Molecular Physiology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 36, Room 2C19, 36 Convent Drive, MSC 4066, Bethesda, MD 20892.(301) 435-5666

swartzk{at}ninds.nih.gov

The gating modifier toxins are a large family of protein toxins that modify either activation or inactivation of voltage-gated ion channels. -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 _1A Ca²⁺ 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 Ca²⁺ channel had no significant effect on inhibition by -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 -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.

Key Words: calcium channels • mutagenesis • agatoxin • voltage-sensing domain

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				E. Redaelli, R. R. Cassulini, D. F. Silva, H. Clement, E. Schiavon, F. Z. Zamudio, G. Odell, A. Arcangeli, J. J. Clare, A. Alagon, et al. Target Promiscuity and Heterogeneous Effects of Tarantula Venom Peptides Affecting Na+ and K+ Ion Channels J. Biol. Chem., February 5, 2010; 285(6): 4130 - 4142. [Abstract] [Full Text] [PDF]

				Y. Xiao, J.-P. Bingham, W. Zhu, E. Moczydlowski, S. Liang, and T. R. Cummins 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., October 3, 2008; 283(40): 27300 - 27313. [Abstract] [Full Text] [PDF]

				M. Milescu, J. Vobecky, S. H. Roh, S. H. Kim, H. J. Jung, J. I. Kim, and K. J. Swartz Tarantula Toxins Interact with Voltage Sensors within Lipid Membranes J. Gen. Physiol., October 29, 2007; 130(5): 497 - 511. [Abstract] [Full Text] [PDF]

				M. Zhang, X.-S. Liu, S. Diochot, M. Lazdunski, and G.-N. Tseng APETx1 from Sea Anemone Anthopleura elegantissima Is a Gating Modifier Peptide Toxin of the Human Ether-a-go-go- Related Potassium Channel Mol. Pharmacol., August 1, 2007; 72(2): 259 - 268. [Abstract] [Full Text] [PDF]

				J. J. Smith, T. R. Cummins, S. Alphy, and K. M. Blumenthal Molecular Interactions of the Gating Modifier Toxin ProTx-II with Nav1.5: IMPLIED EXISTENCE OF A NOVEL TOXIN BINDING SITE COUPLED TO ACTIVATION J. Biol. Chem., April 27, 2007; 282(17): 12687 - 12697. [Abstract] [Full Text] [PDF]

				S. Cestele, V. Yarov-Yarovoy, Y. Qu, F. Sampieri, T. Scheuer, and W. A. Catterall Structure and Function of the Voltage Sensor of Sodium Channels Probed by a beta-Scorpion Toxin J. Biol. Chem., July 28, 2006; 281(30): 21332 - 21344. [Abstract] [Full Text] [PDF]

				S. Kaja, R. C. G. Van de Ven, M. D. Ferrari, R. R. Frants, A. M.J.M. Van den Maagdenberg, and J. J. Plomp Compensatory Contribution of Cav2.3 Channels to Acetylcholine Release at the Neuromuscular Junction of Tottering Mice J Neurophysiol, April 1, 2006; 95(4): 2698 - 2704. [Abstract] [Full Text] [PDF]

				F. Bosmans, L. Rash, S. Zhu, S. Diochot, M. Lazdunski, P. Escoubas, and J. Tytgat Four Novel Tarantula Toxins as Selective Modulators of Voltage-Gated Sodium Channel Subtypes Mol. Pharmacol., February 1, 2006; 69(2): 419 - 429. [Abstract] [Full Text] [PDF]

				S. Y. M. Yeung, D. Thompson, Z. Wang, D. Fedida, and B. Robertson Modulation of Kv3 Subfamily Potassium Currents by the Sea Anemone Toxin BDS: Significance for CNS and Biophysical Studies J. Neurosci., September 21, 2005; 25(38): 8735 - 8745. [Abstract] [Full Text] [PDF]

				J. M. Wang, S. H. Roh, S. Kim, C. W. Lee, J. I. Kim, and K. J. Swartz Molecular Surface of Tarantula Toxins Interacting with Voltage Sensors in Kv Channels J. Gen. Physiol., March 29, 2004; 123(4): 455 - 467. [Abstract] [Full Text] [PDF]

				R. L. Brown, L. L. Lynch, T. L. Haley, and R. Arsanjani Pseudechetoxin Binds to the Pore Turret of Cyclic Nucleotide-gated Ion Channels J. Gen. Physiol., November 24, 2003; 122(6): 749 - 760. [Abstract] [Full Text] [PDF]

				M. C. Sanguinetti and P. B. Bennett Antiarrhythmic Drug Target Choices and Screening Circ. Res., September 19, 2003; 93(6): 491 - 499. [Abstract] [Full Text] [PDF]

				W. P. Kelley, A. M. Wolters, J. T. Sack, R. A. Jockusch, J. C. Jurchen, E. R. Williams, J. V. Sweedler, and W. F. Gilly Characterization of a Novel Gastropod Toxin (6-Bromo-2-mercaptotryptamine) That Inhibits Shaker K Channel Activity J. Biol. Chem., September 12, 2003; 278(37): 34934 - 34942. [Abstract] [Full Text] [PDF]

				J. Wang, J. J. Salata, and P. B. Bennett Saxitoxin Is a Gating Modifier of hERG K+ Channels J. Gen. Physiol., May 27, 2003; 121(6): 583 - 598. [Abstract] [Full Text] [PDF]

				R. E. Oswald, T. M. Suchyna, R. McFeeters, P. Gottlieb, and F. Sachs Solution Structure of Peptide Toxins That Block Mechanosensitive Ion Channels J. Biol. Chem., September 6, 2002; 277(37): 34443 - 34450. [Abstract] [Full Text] [PDF]

				P. Escoubas, S. Diochot, M.-L. Celerier, T. Nakajima, and M. Lazdunski Novel Tarantula Toxins for Subtypes of Voltage-Dependent Potassium Channels in the Kv2 and Kv4 Subfamilies Mol. Pharmacol., July 1, 2002; 62(1): 48 - 57. [Abstract] [Full Text] [PDF]

				S. S. Sidach and I. M. Mintz Kurtoxin, A Gating Modifier of Neuronal High- and Low-Threshold Ca Channels J. Neurosci., March 15, 2002; 22(6): 2023 - 2034. [Abstract] [Full Text] [PDF]

				J. P. Johnson Jr, J. R. Balser, and P. B. Bennett A Novel Extracellular Calcium Sensing Mechanism in Voltage-Gated Potassium Ion Channels J. Neurosci., June 15, 2001; 21(12): 4143 - 4153. [Abstract] [Full Text] [PDF]

				H. Chen and S. H. Heinemann Interaction of Scorpion {alpha}-Toxins with Cardiac Sodium Channels: Binding Properties and Enhancement of Slow Inactivation J. Gen. Physiol., June 1, 2001; 117(6): 505 - 518. [Abstract] [Full Text] [PDF]

				Y. Li-Smerin and K. J. Swartz Helical Structure of the Cooh Terminus of S3 and Its Contribution to the Gating Modifier Toxin Receptor in Voltage-Gated Ion Channels J. Gen. Physiol., March 1, 2001; 117(3): 205 - 218. [Abstract] [Full Text] [PDF]

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents