Molecular architecture of the fungal-specific potassium channel TOK1.

Abstract

In Candida albicans, potassium (K⁺) channels fine-tune ionic balance under stress, contributing to host colonization. Fungal two-pore domain, outwardly rectifying potassium (TOK) channels remain insufficiently characterized despite evidence implicating them in growth and viability. Here, we describe the atomic-resolution structure of a fungal potassium channel, TOK1 from C. albicans (CaTOK), revealing an architecture defined by eight transmembrane helices and a membrane topology distinct from previously characterized K⁺ channel classes. The first four helices form a tetraspanin-like bundle resembling auxiliary subunits of human neuronal ion channels. The pore features an inner helical gating movement analogous to mammalian dimeric K⁺ channels, while the K⁺ selectivity filter exhibits atypical ion coordination. A cytosolic C-terminal bundle forms an intramolecular network that likely stabilizes CaTOK and may mediate gating. These findings provide a framework for understanding TOK channel function and facilitate future studies of fungal ion homeostasis, pathogenicity, and therapeutic development.