TY  - JOUR
AU  - Kowal, Julia
AU  - Chami, Mohamed
AU  - Baumgartner, Paul
AU  - Arheit, Marcel
AU  - Chiu, Po-Lin
AU  - Rangl, Martina
AU  - Scheuring, Simon
AU  - Schröder, Gunnar F.
AU  - Nimigean, Crina M.
AU  - Stahlberg, Henning
TI  - Ligand-induced structural changes in the cyclic nucleotide-modulated potassium channel MloK1
JO  - Nature Communications
VL  - 5
SN  - 2041-1723
CY  - London
PB  - Nature Publishing Group
M1  - FZJ-2014-02989
SP  - (1-10) 4106
PY  - 2014
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000331084400015
C6  - pmid:24469021
DO  - DOI:10.1038/ncomms4106
UR  - https://juser.fz-juelich.de/record/153358
ER  -