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

Author

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  • 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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    Cited by:

    1. Verena Burtscher & Jonathan Mount & Jian Huang & John Cowgill & Yongchang Chang & Kathleen Bickel & Jianhan Chen & Peng Yuan & Baron Chanda, 2024. "Structural basis for hyperpolarization-dependent opening of human HCN1 channel," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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