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Publication Abstract from PubMed

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.

Ligand-induced structural changes in the cyclic nucleotide-modulated potassium channel MloK1.,Kowal J, Chami M, Baumgartner P, Arheit M, Chiu PL, Rangl M, Scheuring S, Schroder GF, Nimigean CM, Stahlberg H Nat Commun. 2014 Jan 28;5:3106. doi: 10.1038/ncomms4106. PMID:24469021^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.