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Ligand-induced structural changes in the cyclic nucleotide-modulated potassium channel MloK1.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Kowal Julia, Chami Mohamed, Baumgartner Paul, Arheit Marcel, Chiu Po-Lin, Rangl Martina, Scheuring Simon, Schröder Gunnar F, Nimigean Crina M, Stahlberg Henning,
Project Electron Microscopy of Membrane Proteins
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Original article (peer-reviewed)

Journal Nature communications
Volume (Issue) 5
Page(s) 3106 - 3106
Title of proceedings Nature communications
DOI 10.1038/ncomms4106


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.