Cross-linking of charybdotoxin to high-conductance calcium-activated potassium channels: identification of the covalently modified toxin residue

Biochemistry
P MunujosM L Garcia

Abstract

High-conductance calcium-activated potassium (maxi-K) channels are composed of two subunits, alpha and beta. The pore-forming alpha subunit is a member of the mSlo family of K+ channels, whereas the beta subunit is a novel protein that modulates the biophysical and pharmacological properties of the channel complex. In the presence of a bifunctional cross-linking reagent, monoiodotyrosine charybdotoxin ([125I]ChTX) is covalently incorporated specifically into Lys69 of the beta subunit, which is located in a large extracellular loop of this protein. Using variants of ChTX which retain their channel-blocking activity and in which individual Lys residues have been mutated, we have identified the corresponding amino acid in ChTX that is involved in the cross-linking reaction. All of the ChTX mutants investigated bind to the maxi-K channel and display the same pharmacological profile as native ChTX in competition binding experiments. Whereas substitution of amino acids at positions 11 and 31 of ChTX yields wild-type cross-linking patterns, the peptide without a Lys at position 32 fails to incorporate into the beta subunit of the maxi-K channel. Given the model for the interaction between ChTX and the outer vestibule of the maxi-K cha...Continue Reading

Citations

Jun 1, 1996·Journal of Bioenergetics and Biomembranes·G J KaczorowskiM L Garcia
May 13, 2010·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Jan FrässdorfMarkus W Hollmann
Oct 29, 1998·Toxicon : Official Journal of the International Society on Toxinology·M L GarciaG J Kaczorowski
Sep 5, 2002·The Journal of Clinical Investigation·Lingyun WuRui Wang
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·M HannerM L Garcia
Mar 28, 1997·The Journal of Biological Chemistry·R Wang, L Wu
Jun 5, 2004·The Journal of Biological Chemistry·Chen-Qi XuCheng-Wu Chi
May 22, 2007·American Journal of Physiology. Heart and Circulatory Physiology·André HeinenAmadou K S Camara
Apr 24, 2003·Experimental Biology and Medicine·Rui Wang, Lingyun Wu
Jun 24, 2004·Journal of the American Chemical Society·Núria VallsJuan A Subirana

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