This title appears in the Scientific Report : 2014 

Ligand-induced structural changes in the cyclic nucleotide-modulated potassium channel MloK1
Kowal, Julia
Chami, Mohamed / Baumgartner, Paul / Arheit, Marcel / Chiu, Po-Lin / Rangl, Martina / Scheuring, Simon / Schröder, Gunnar F. / Nimigean, Crina M. (Corresponding Author) / Stahlberg, Henning
Strukturbiochemie ; ICS-6
Nature Communications, 5 (2014) S. (1-10) 4106
London Nature Publishing Group 2014
10.1038/ncomms4106
24469021
Journal Article
Structural Biology
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OpenAccess
Please use the identifier: http://hdl.handle.net/2128/24475 in citations.
Please use the identifier: http://dx.doi.org/10.1038/ncomms4106 in citations.
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.