%0 Journal Article
%A Kowal, Julia
%A Chami, Mohamed
%A Baumgartner, Paul
%A Arheit, Marcel
%A Chiu, Po-Lin
%A Rangl, Martina
%A Scheuring, Simon
%A Schröder, Gunnar F.
%A Nimigean, Crina M.
%A Stahlberg, Henning
%T Ligand-induced structural changes in the cyclic nucleotide-modulated potassium channel MloK1
%J Nature Communications
%V 5
%@ 2041-1723
%C London
%I Nature Publishing Group
%M FZJ-2014-02989
%P (1-10) 4106
%D 2014
%X Cyclic nucleotide-modulated ion channels are important for signal transduction and pacemaking in eukaryotes. The molecular determinants of ligand gating in these channels are still unknown, mainly because of a lack of direct structural information. Here we report ligand-induced conformational changes in full-length MloK1, a cyclic nucleotide-modulated potassium channel from the bacterium Mesorhizobium loti, analysed by electron crystallography and atomic force microscopy. Upon cAMP binding, the cyclic nucleotide-binding domains move vertically towards the membrane, and directly contact the S1–S4 voltage sensor domains. This is accompanied by a significant shift and tilt of the voltage sensor domain helices. In both states, the inner pore-lining helices are in an ‘open’ conformation. We propose a mechanism in which ligand binding can favour pore opening via a direct interaction between the cyclic nucleotide-binding domains and voltage sensors. This offers a simple mechanistic hypothesis for the coupling between ligand gating and voltage sensing in eukaryotic HCN channels.
%F PUB:(DE-HGF)16
%9 Journal Article
%U <Go to ISI:>//WOS:000331084400015
%$ pmid:24469021
%R 10.1038/ncomms4106
%U https://juser.fz-juelich.de/record/153358