Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR
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Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR. / Lange, Adam; Giller, Karin; Hornig, Sönke; Martin-Eauclaire, Marie-France; Pongs, Olaf; Becker, Stefan; Baldus, Marc.
in: NATURE, Jahrgang 440, Nr. 7086, 13.04.2006, S. 959-62.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR
AU - Lange, Adam
AU - Giller, Karin
AU - Hornig, Sönke
AU - Martin-Eauclaire, Marie-France
AU - Pongs, Olaf
AU - Becker, Stefan
AU - Baldus, Marc
PY - 2006/4/13
Y1 - 2006/4/13
N2 - 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.
AB - 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.
KW - Amino Acid Sequence
KW - Animals
KW - Bacterial Proteins
KW - Kv1.3 Potassium Channel
KW - Models, Molecular
KW - Molecular Sequence Data
KW - Mutation
KW - Nuclear Magnetic Resonance, Biomolecular
KW - Oocytes
KW - Potassium Channel Blockers
KW - Potassium Channels
KW - Protein Conformation
KW - Recombinant Fusion Proteins
KW - Scorpion Venoms
KW - Scorpions
KW - Xenopus
U2 - 10.1038/nature04649
DO - 10.1038/nature04649
M3 - SCORING: Journal article
C2 - 16612389
VL - 440
SP - 959
EP - 962
JO - NATURE
JF - NATURE
SN - 0028-0836
IS - 7086
ER -