Download MendeleyLigand-induced structural changes in the cyclic nucleotide-modulated potassium channel MloK1.
Kowal, J., Chami, M., Baumgartner, P., Arheit, M., Chiu, P.L., Rangl, M., Scheuring, S., Schroder, G.F., Nimigean, C.M., Stahlberg, H.(2014) Nat Commun 5: 3106-3106
- PubMed: 24469021
- DOI: https://doi.org/10.1038/ncomms4106
- Primary Citation of Related Structures:
4CHV, 4CHW - PubMed 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.
Organizational Affiliation:
Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.
