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

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.

AtKC1 and CIPK23 Synergistically Modulate AKT1-Mediated Low-Potassium Stress Responses in Arabidopsis

“…The structure of the AKT1/AtKC1 open state was modeled using MlotiK1 protein from Mesorhizobium loti (Protein Data Bank no. 4CHV, chain A) as the template (Kowal et al, 2014). The structure of the AKT1/AtKC1 closed state was modeled using MlotiK1 (Protein Data Bank no.…”

Evidence for the Involvement of Potassium Channel Inhibition in the Antidepressant-Like Effects of Hesperidin in the Tail Suspension Test in Mice

“…7 Potassium (K + ) channels are a key component of this electrical circuit and are controlled either by an electrical impulse or through signaling molecules. 8 The association of K + channels in the modulation of depression has been suggested by several preclinical studies. The administration of different K + channel inhibitors such as tetraethylammonium (TEA), gliquidone and glibenclamide, charybdotoxin and apamin decreases the duration of immobility in the forced swimming test (FST) in mice, which is an indicative of an antidepressant-like effect.…”

Directly watching biomolecules in action by high-speed atomic force microscopy

“…From this observation, it was revealed that this inter-trimer bR-bR contact engenders both positive and (Ruan et al 2017) Height change in MloK1 cyclic nucleotide-modulated channels (Kowal et al 2014;Rangl et al 2016) Spiral spring formation by ESCRT protein (Chiaruttini et al 2015) Stiffness map of membrane protein moieties estimated from thermal motion (Preiner et al 2015) Diffusion and interaction of outer membrane protein F (OmpF) (Casuso et al 2012) Bacteriorhodopsin responding to light Yamashita et al 2013) ATP-induced height change of Ca 2+ pump (Yokokawa and Takeyasu Moving net-like structure formed by prion covering living bacterial surface (Yamashita et al 2012;Oestreicher et al 2015) Dynamic morphological changes in living cells (Shibata et al 2015) Dynamics of nucleoporins inside nuclear porin complexes of Xenopus laevis oocytes (Sakiyama et al 2016) Responses of bacteria to antimicrobial peptide (Fantner et al 2010) a Personal communications negative cooperative effects in the decay kinetics as the initial bR recovers. Further HS-AFM studies of bR successfully revealed how bR molecules form trimers and why the trimer formation is required for the function of bR (Yamashita et al 2013).…”