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 () and Henning Stahlberg ()
Additional contact information
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
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
Crina M. Nimigean: Physiology and Biophysics, and Biochemistry, Weill Cornell Medical College
Henning Stahlberg: Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: 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.

Date: 2014
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms4106 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4106

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms4106

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().