PMID: 8938722Jan 1, 1996Paper

Interaction of Ca2(+)-activated K+ channels with refolded charybdotoxins mutated at a central interaction residue

Neuropharmacology
A A NainiC Miller

Abstract

Charybdotoxin is a small peptide blocker of K+ channels, rigidly held in active conformation by three disulfide bonds. The toxin blocks K+ channels by binding to a receptor site located at the external "vestibule", and thus physically occluding the outer opening of the K+ conduction pore. In the blocked complex, K27, a residue on the toxin's molecular surface, projects its epsilon-amino group into the K(+)-selective pore. The results here show that CTX, produced by heterologous expression in E. coli, may be manipulated to place unnatural positively charged residues at position 27. The toxin folds faithfully to its native conformation when the crucial lysine at position 27 is replaced by a cysteine residue, a maneuver that allows specific chemical modification of this side-chain. Replacements of K27 by side-chains slightly shorter or slightly longer than lysine yield active toxins. The toxin variant with ornithine at this position interacts much less strongly with K+ ions in the pore of slowpoke-type Ca2(+)-activated K+ channels than does wild-type toxin. This result argues that the epsilon-amino group of K27 in bound toxin lies only a few ångstroms away from a K+ ion occupying the blocked pore. The peptide folds with high effic...Continue Reading

References

Apr 5, 1979·Journal of Molecular Biology·T E Creighton
Apr 1, 1992·Biophysical Journal·P StampeC Miller
Mar 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·C S ParkC Miller
Mar 1, 1988·The Journal of General Physiology·R MacKinnon, C Miller
Jan 1, 1988·Annual Review of Biophysics and Biophysical Chemistry·D P Goldenberg
Jul 20, 1973·Science·C B Anfinsen
Oct 1, 1993·Biophysical Journal·S A Goldstein, C Miller
Apr 1, 1994·Protein Engineering·E ShimonyC Miller
Sep 27, 1994·Proceedings of the National Academy of Sciences of the United States of America·M Stocker, C Miller
Oct 19, 1993·Biochemistry·K Ramalingam, G H Snyder

❮ Previous
Next ❯

Citations

Jul 16, 2003·The Journal of General Physiology·Paul K KienkerAlan Finkelstein
Sep 13, 2013·Channels·Gustavo F ContrerasRamón Latorre

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiac Conduction System

The cardiac conduction system is a specialized tract of myocardial cells responsible for maintaining normal cardiac rhythm. Discover the latest research on the cardiac conduction system here.