Author
Listed:
- Julia Kowal
(Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel)
- Mohamed Chami
(Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel)
- Paul Baumgartner
(Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel)
- Marcel Arheit
(Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel)
- Po-Lin Chiu
(Molecular and Cellular Biology, CBS, UC Davis, Davis, California 95616, USA
Present address: Harvard Medical School, Boston, Massachusetts 02115, USA)
- Martina Rangl
(U1006 INSERM, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy)
- Simon Scheuring
(U1006 INSERM, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy)
- Gunnar F. Schröder
(Forschungszentrum Jülich, Institute of Complex Systems, ICS-6: Structural Biochemistry
Heinrich-Heine University Düsseldorf)
- Crina M. Nimigean
(Physiology and Biophysics, and Biochemistry, Weill Cornell Medical College)
- Henning Stahlberg
(Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel)
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.
Suggested Citation
Julia Kowal & Mohamed Chami & Paul Baumgartner & Marcel Arheit & Po-Lin Chiu & Martina Rangl & Simon Scheuring & Gunnar F. Schröder & Crina M. Nimigean & Henning Stahlberg, 2014.
"Ligand-induced structural changes in the cyclic nucleotide-modulated potassium channel MloK1,"
Nature Communications, Nature, vol. 5(1), pages 1-10, May.
Handle:
RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4106
DOI: 10.1038/ncomms4106
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