TY - JOUR
T1 - The molecular mechanism of toxin-induced conformational changes in a potassium channel
T2 - relation to C-Type inactivation
AU - Zachariae, Ulrich
AU - Schneider, Robert
AU - Velisetty, Phanindra
AU - Lange, Adam
AU - Seeliger, Daniel
AU - Wacker, Sören J.
AU - Karimi-Nejad, Yasmin
AU - Vriend, Gert
AU - Becker, Stefan
AU - Pongs, Olaf
AU - Baldus, Marc
AU - de Groot, Bert L.
N1 - MEDLINE® is the source for the MeSH terms of this document.
PY - 2008
Y1 - 2008
N2 - Recently, a solid-state NMR study revealed that scorpion toxin binding leads to conformational changes in the selectivity filter of potassium channels. The exact nature of the conformational changes, however, remained elusive. We carried out all-atom molecular dynamics simulations that enabled us to cover the complete pathway of toxin approach and binding, and we validated our simulation results by using solid-state NMR data and electrophysiological measurements. Our structural model revealed a mechanism of cooperative toxin-induced conformational changes that accounts both for the signal changes observed in solid-state NMR and for the tight interaction between KcsA-Kv1.3 and Kaliotoxin. We show that this mechanism is structurally and functionally closely related to recovery from C-type inactivation. Furthermore, our simulations indicate heterogeneity in the binding modes of Kaliotoxin, which might serve to enhance its affinity for KcsA-Kv1.3 further by entropic stabilization.
AB - Recently, a solid-state NMR study revealed that scorpion toxin binding leads to conformational changes in the selectivity filter of potassium channels. The exact nature of the conformational changes, however, remained elusive. We carried out all-atom molecular dynamics simulations that enabled us to cover the complete pathway of toxin approach and binding, and we validated our simulation results by using solid-state NMR data and electrophysiological measurements. Our structural model revealed a mechanism of cooperative toxin-induced conformational changes that accounts both for the signal changes observed in solid-state NMR and for the tight interaction between KcsA-Kv1.3 and Kaliotoxin. We show that this mechanism is structurally and functionally closely related to recovery from C-type inactivation. Furthermore, our simulations indicate heterogeneity in the binding modes of Kaliotoxin, which might serve to enhance its affinity for KcsA-Kv1.3 further by entropic stabilization.
UR - http://www.scopus.com/inward/record.url?scp=42949094850&partnerID=8YFLogxK
U2 - 10.1016/j.str.2008.01.018
DO - 10.1016/j.str.2008.01.018
M3 - Article
C2 - 18462679
AN - SCOPUS:42949094850
SN - 0969-2126
VL - 16
SP - 747
EP - 754
JO - Structure
JF - Structure
IS - 5
ER -