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-Structure paper
Title | Ligand-induced structural changes in the cyclic nucleotide-modulated potassium channel MloK1. |
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Journal, issue, pages | Nat Commun, Vol. 5, Page 3106, Year 2014 |
Publish date | Oct 27, 2015 |
Authors | Julia Kowal / Mohamed Chami / Paul Baumgartner / Marcel Arheit / Po-Lin Chiu / Martina Rangl / Simon Scheuring / Gunnar F Schröder / Crina M Nimigean / Henning Stahlberg / |
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 ...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. |
External links | Nat Commun / PubMed:24469021 / PubMed Central |
Methods | EM (electron crystallography) |
Resolution | 7.0 Å |
Structure data | |
Chemicals | ChemComp-K: |
Source |
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Keywords | TRANSPORT / 2DX / VOLTAGE GATED POTASSIUM CHANNEL / CNBD / 2D CRYSTAL / TRANSPORT PROTEIN |