Referenced in: none

Automatically associated channels: Kv1.3

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

Authors: Adam Lange, Karin Giller, Sönke Hornig, Marie-France Martin-Eauclaire, Olaf Pongs, Stefan Becker, Marc Baldus

Journal, date & volume: Nature, 2006 Apr 13 , 440, 959-62

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16612389

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 toxin-K+ channel interactions.