Voltage-gated proton channels from fungi highlight role of peripheral regions in channel activation

Abstract

Here, we report the identification and characterization of the first proton channels from fungi. The fungal proteins are related to animal voltage-gated Hv channels and are conserved in both higher and lower fungi. Channels from Basidiomycota and Ascomycota appear to be evolutionally and functionally distinct. Representatives from the two phyla share several features with their animal counterparts, including structural organization and strong proton selectivity, but they differ from each other and from animal Hvs in terms of voltage range of activation, pharmacology, and pH sensitivity. The activation gate of Hv channels is believed to be contained within the transmembrane core of the protein and little is known about contributions of peripheral regions to the activation mechanism. Using a chimeragenesis approach, we find that intra- and extracellular peripheral regions are main determinants of the voltage range of activation in fungal channels, highlighting the role of these overlooked components in channel gating.

Activation-pathway transitions in human voltage-gated proton channels revealed by a non-canonical fluorescent amino acid

“…It was shown that for every unit of ΔpH, the voltage of mid-activation shifts ~40 mV. Subsequently, all native and cloned proton channels have been found to approximately follow this rule ( Sasaki et al, 2006 ; Ramsey et al, 2006 ; Rangel-Yescas et al, 2021 ; Musset et al, 2008 ; Smith et al, 2011 ; Zhao and Tombola, 2021 ). Recent experiments suggest that the proton gradient produces this effect by acting on the voltage sensor and not only affecting a close-to-open transition since gating currents and channel opening are similarly modulated ( Schladt and Berger, 2020 ; Carmona et al, 2021 ).…”

The effect of rhamnolipids on fungal membrane models as described by their interactions with phospholipids and sterols: An in silico study

“…The gating kinetics of voltage-gated ion channels can also be altered by the modulation of ΨD. This mechanism of action is employed by some antifungal agents ( Zakharova et al, 2019 ) due to the fact that ΨD is important for fungal survival ( Zhao and Tombola, 2021 ), as in eukaryotes for the regulation of cardiac or neuronal processes ( Brockman, 1994 ; Pearlstein, Dickson, and Hornak, 2017 ).…”

Proton channels in molluscs: A new bivalvian‐specific minimal HV4 channel

“…Interestingly, the pH regulation of the conductance in CgH V 4 is higher than the rule of forty (40 mV/pH) for most of the measured H V channels [15,45] but is comparable to that of H V insect channels [19,20]. Compared to other molluscan H V channels, CgH V 4 shows a pH sensitivity slightly stronger than the molluscan Aplysia californica H V 1 and H V 2 channels (~ 45 mV/pH) [17] but still weaker than the anomalously high sensitivity of Helisoma trivolvis (60 mV/pH at pH o 5–7) [46] and fungal channels (80–90 mV/pH) [5]. The similitude of pH‐dependent gating of H V channels from different species is per se of interest since it proposes a common mechanism of pH‐coupled gating that is still unknown.…”

“…Ala, Ser, and Asn). For those fungal channels that were tested, the ΔpH‐gating deviated largely from the rule of forty [5]. In H V 4 channels, the species Scapharca broughtonii and Perna canaliculus have glutamine (Gln 107 ) and asparagine (Asn 104 ) residues, respectively.…”