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

Julia Kowal, Mohamed Chami, Paul Baumgartner, Marcel Arheit, Po Lin Chiu, Martina Rangl, Simon Scheuring, Gunnar F. Schröder, Crina M. Nimigean, Henning Stahlberg

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number3106
JournalNature communications
Volume5
DOIs
StatePublished - Jan 28 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Kowal, J., Chami, M., Baumgartner, P., Arheit, M., Chiu, P. L., Rangl, M., Scheuring, S., Schröder, G. F., Nimigean, C. M., & Stahlberg, H. (2014). Ligand-induced structural changes in the cyclic nucleotide-modulated potassium channel MloK1. Nature communications, 5, [3106]. https://doi.org/10.1038/ncomms4106