Subtype specificity of scorpion beta-toxin Tz1 interaction with voltage-gated sodium channels is determined by the pore loop of domain 3

Molecular Pharmacology
Enrico LeipoldStefan H Heinemann

Abstract

Voltage-gated sodium (Nav) channels are modulated by a variety of specific neurotoxins. Scorpion beta-toxins affect the voltage-dependence of channel gating: In their presence, Nav channels activate at subthreshold membrane voltages. Previous mutagenesis studies have revealed that the beta-toxin Css4 interacts with the extracellular linker between segments 3 and 4 in domain 2 of Nav channels with the effect to trap this voltage sensor in an open position (Neuron 21: 919-931, 1998 ). The voltage sensor of domain 2 was thus identified to constitute a major part of neurotoxin receptor site 4. In this work, we studied the effects of the beta-toxin Tz1 from the Venezuelan scorpion Tityus zulianus on various mammalian Nav channel types expressed in HEK 293 cells. Although skeletal muscle channels (Nav1.4) were strongly affected by Tz1, the neuronal channels Nav1.6 and Nav1.2 were less sensitive, and the cardiac Nav1.5 and the peripheral nerve channel Nav1.7 were essentially insensitive. Analysis of channel chimeras in which whole domains of Nav1.2 were inserted into a Nav1.4 background revealed that the Nav1.2 phenotype was not conferred to Nav1.4 by domain 2 but by domain 3. The interaction epitope could be narrowed down to residues...Continue Reading

References

Jan 25, 1992·Proceedings of the National Academy of Sciences of the United States of America·M E GellensR G Kallen
Oct 1, 1992·Physiological Reviews·W A Catterall
Sep 22, 1999·European Journal of Biochemistry·L D PossaniJ Tytgat
Jun 5, 2002·Journal of Neuroscience Methods·Andre R MassensiniMarco A Romano-Silva
Apr 28, 2004·Toxicon : Official Journal of the International Society on Toxinology·Adolfo BorgesStefan H Heinemann
Mar 1, 2005·Toxicon : Official Journal of the International Society on Toxinology·Frank BosmansJan Tytgat
Jul 9, 2005·Science·Stephen B LongRoderick Mackinnon
Jul 16, 2005·The Journal of Physiology·Massimo Mantegazza, Sandrine Cestèle

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Citations

Aug 31, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jinti WangWilliam A Catterall
Apr 12, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ruth SittlRichard W Carr
Jul 5, 2012·The Journal of Biological Chemistry·Joel Z ZhangWilliam A Catterall
Mar 28, 2012·The Journal of General Physiology·Enrico LeipoldStefan H Heinemann
Feb 11, 2014·European Journal of Pharmacology·Jan M BraunerTobias Huth
Mar 2, 2010·The Journal of Biological Chemistry·Sébastien Dutertre, Richard J Lewis
Dec 23, 2015·Toxins·Nehan R Munasinghe, MacDonald J Christie
Dec 30, 2015·The Journal of General Physiology·Christopher A AhernBaron Chanda
Jan 28, 2015·The Journal of General Physiology·Marie-France Martin-EauclairePierre E Bougis
Jun 18, 2015·PloS One·Thalita S CamargosElisabeth F Schwartz
Jul 29, 2008·Toxicon : Official Journal of the International Society on Toxinology·Gabrielle B EdgertonDorothy A Hanck
Apr 28, 2012·Toxicon : Official Journal of the International Society on Toxinology·Christopher J Bohlen, David Julius
Aug 23, 2018·Toxins·Daniel Oliveira da MataElisabeth Ferroni Schwartz
Aug 10, 2007·The Journal of Biological Chemistry·Lior CohenMichael Gurevitz
Jul 31, 2013·American Journal of Physiology. Heart and Circulatory Physiology·Michael F SheetsDorothy A Hanck
Mar 13, 2012·Pharmacological Reviews·Richard J LewisMacDonald J Christie
Nov 18, 2008·Expert Opinion on Investigational Drugs·Steve England
Aug 31, 2017·PloS One·Bradley H HoppKhaleel A Razak
Aug 23, 2018·Frontiers in Pharmacology·Denis B Tikhonov, Boris S Zhorov
Jun 27, 2019·Marine Drugs·Harry Morales DuqueOctávio Luiz Franco
Nov 23, 2018·Biochimica Et Biophysica Acta. Biomembranes·Diogo Vieira TiberyElisabeth Ferroni Schwartz
Nov 4, 2006·Toxicon : Official Journal of the International Society on Toxinology·Ricardo C Rodríguez de la Vega, Lourival D Possani
Jan 2, 2007·Toxicon : Official Journal of the International Society on Toxinology·Michael GurevitzDalia Gordon
Jan 12, 2007·Toxicon : Official Journal of the International Society on Toxinology·Dalia GordonMichael Gurevitz
Jan 24, 2007·Toxicon : Official Journal of the International Society on Toxinology·William A CatterallTodd Scheuer
Apr 5, 2012·The Journal of Physical Chemistry. B·Rong Chen, Shin-Ho Chung
Oct 9, 2007·Toxicon : Official Journal of the International Society on Toxinology·Adolfo BorgesCarlos Chávez-Olórtegui
Oct 9, 2008·Biochemical Pharmacology·Meichi WangSongping Liang
Mar 10, 2009·Toxicon : Official Journal of the International Society on Toxinology·Yehu MoranMichael Gurevitz
Oct 30, 2016·Neuropharmacology·David M HousleyErnest A Jennings
Feb 22, 2011·Peptides·Najwa AbbasMarie-France Martin-Eauclaire
Nov 17, 2011·Toxicon : Official Journal of the International Society on Toxinology·Ernesto TrejoMarcelo J Alfonzo
Jun 15, 2012·Toxicon : Official Journal of the International Society on Toxinology·Michael Gurevitz

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