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

42 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Cyclic Nucleotides
Potassium Channels
nucleotides
Ligands
ligands
Electric potential
electric potential
helices
sensors
Sensors
Mesorhizobium
eukaryotes
porosity
Signal transduction
Crystallography
Atomic Force Microscopy
linings
Eukaryota
Ion Channels
Linings

ASJC Scopus subject areas

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

Cite this

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.; Stahlberg, Henning.

In: Nature Communications, Vol. 5, 3106, 28.01.2014.

Research output: Contribution to journalArticle

Kowal, J, Chami, M, Baumgartner, P, Arheit, M, Chiu, P-L, Rangl, M, Scheuring, S, Schröder, GF, Nimigean, CM & Stahlberg, H 2014, 'Ligand-induced structural changes in the cyclic nucleotide-modulated potassium channel MloK1', Nature Communications, vol. 5, 3106. https://doi.org/10.1038/ncomms4106
Kowal, Julia ; Chami, Mohamed ; Baumgartner, Paul ; Arheit, Marcel ; Chiu, Po-Lin ; Rangl, Martina ; Scheuring, Simon ; Schröder, Gunnar F. ; Nimigean, Crina M. ; Stahlberg, Henning. / Ligand-induced structural changes in the cyclic nucleotide-modulated potassium channel MloK1. In: Nature Communications. 2014 ; Vol. 5.
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