Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR

Nature
Adam LangeMarc Baldus

Abstract

The active site of potassium (K+) channels catalyses the transport of K+ ions across the plasma membrane--similar to the catalytic function of the active site of an enzyme--and is inhibited by toxins from scorpion venom. On the basis of the conserved structures of K+ pore regions and scorpion toxins, detailed structures for the K+ channel-scorpion toxin binding interface have been proposed. In these models and in previous solution-state nuclear magnetic resonance (NMR) studies using detergent-solubilized membrane proteins, scorpion toxins were docked to the extracellular entrance of the K+ channel pore assuming rigid, preformed binding sites. Using high-resolution solid-state NMR spectroscopy, here we show that high-affinity binding of the scorpion toxin kaliotoxin to a chimaeric K+ channel (KcsA-Kv1.3) is associated with significant structural rearrangements in both molecules. Our approach involves a combined analysis of chemical shifts and proton-proton distances and demonstrates that solid-state NMR is a sensitive method for analysing the structure of a membrane protein-inhibitor complex. We propose that structural flexibility of the K+ channel and the toxin represents an important determinant for the high specificity of tox...Continue Reading

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Citations

Sep 3, 2013·European Biophysics Journal : EBJ·Timothy A CrossAnthony Watts
Mar 15, 2008·Applied Microbiology and Biotechnology·Stefan Becker, Heinrich Terlau
Oct 13, 2006·Journal of Biomolecular NMR·Stefan JehleBarth-Jan van Rossum
Feb 24, 2007·Journal of Biomolecular NMR·Karla WernerH Gobind Khorana
Jul 28, 2007·Journal of Biomolecular NMR·Marc Baldus
Aug 10, 2007·Journal of Biomolecular NMR·W Trent FranksChad M Rienstra
Nov 23, 2011·Journal of Biomolecular NMR·Deepak NandMarc Baldus
Dec 15, 2011·Journal of Biomolecular NMR·Rasmus Linser
Aug 21, 2013·Solid State Nuclear Magnetic Resonance·Ming ShenQun Chen
Apr 17, 2013·Accounts of Chemical Research·Markus Weingarth, Marc Baldus
Mar 19, 2013·Accounts of Chemical Research·Antoine LoquetAdam Lange
Mar 9, 2013·Accounts of Chemical Research·Dylan T MurrayTimothy A Cross
Jun 12, 2013·Accounts of Chemical Research·Sandra J Ullrich, Clemens Glaubitz
Nov 17, 2012·Chemical Reviews·Joseph W F RobertsonSoojay Banerjee
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