TOK channels use the two gates in classical K ⁺ channels to achieve outward rectification

Abstract

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Secrets of the fungus-specific potassium channel TOK family

“…In all three closed situations, outward currents were not enabled. This model nicely explained the dependence on K + concentrations at both sides of the membrane and was validated by experimental data with different TOKs from pathogenic fungi and yeasts and with channel mutants [44]. Similarly, gating via the selective pore (C-type gating) was recently described in a structural study of a representative member of the animal two-pore channels [59].…”

“…Regarding the activity of TOK channels in other yeast species (C. albicans and C. neoformans), H99TOK channels are strictly selective for K + while CnTOK and CaTOK transport K + and Na + [44]. H99TOK showed small inward currents at potentials below EK.…”

“…If this were the case, K + permeation would indeed depend on both K + concentrations, rather than the gradient between them. In this context, a relatively simple gating model was more recently developed based on the assumption of ion binding sites in the pore domain, at the pore entry, within the pore, and at an inner cavity, as well as on the interaction of two independent gating mechanisms [44]. K + concentrations would determine the ion occupancy of the binding sites, thus playing a role in the K + -dependent gating, and the membrane potential would determine the internal gate.…”

“…neoformans), and H99TOK (C. neoformans var. grubii) [33,41,44]. Interestingly, compared to the other TOKs, the CnTOK and H99TOK of C. neoformans display flipped pore domains, GYGD in pore #2 and GFGD as pore #1, like the animal 4-TM two-pore channels K2P.…”

In Silico Predictions of Ecological Plasticity Mediated by Protein Family Expansions in Early-Diverging Fungi

“…The voltage-gated ion channel (VIC) superfamily (1.A.1) occurs abundantly in Neocallimastigomycota and Glomeromycotina. There are two described VIC proteins in fungi, both from Saccharomyces cerevisiae: TOK1, which is an outwardly rectifying K+ channel with a unique structure and function [122], and calcium channel protein Cch1, which is essential for a full response to ion stress [123].…”