BPS2026 - Structural basis of the TOK1 potassium channel from Candida albicans

Many fungi utilize high turgor pressure for morphogenesis, requiring tight regulation of ionic gradients. Ion regulation is important for pathogenesis, reproduction, and general homeostasis across the fungal kingdom. In the major human fungal pathogen Candida albicans , potassium (K + ) channels fine-tune ionic balance under stressful environmental conditions, contributing to colonization of the human host. Two-pore domain, outwardly rectifying potassium (TOK) channels, uniquely found in fungi, remain insufficiently characterized despite early evidence implicating them in diverse intracellular processes essential for cellular growth and viability, and their potential as antifungal targets. Here, we describe the first atomic resolution structure of a fungal potassium channel—TOK1 from C. albicans (CaTOK)—revealing a membrane topology distinct from all other known K + channel classes. We propose that CaTOK1 utilizes two unique regions—TOK auxiliary subunit-like channel (TALC) domain and a structured c-terminal bundle—to regulate TOK1 gating. Conformational analysis of TOK1 pore features an inner helical gating mechanism with “up” and “down” conformations similar to mammalian dimeric K + channels. These findings provide a structural framework for understanding TOK channel activity and lay the groundwork for future studies on fungal ion homeostasis, pathogenicity, and therapeutic development.