BPS2026 – Molecular architecture of the fungal-specific potassium channel TOK1

Brice Durocher; Rían W. Manville; Rui Yan; Zhiheng Yu; Geoffrey W. Abbott; Alexandria N. Miller

doi:10.1016/j.bpj.2025.11.316

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BPS2026 – Molecular architecture of the fungal-specific potassium channel TOK1

Abstract

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BPS2026 – Molecular architecture of the fungal-specific potassium channel TOK1

Brice Durocher, Rían W. Manville, Rui Yan, Zhiheng Yu, Geoffrey W. Abbott and Alexandria N. Miller

Biophysical journal, Vol.125(4 Supplement 1), p.20

02/2026

DOI: 10.1016/j.bpj.2025.11.316

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Abstract

Potassium (K+) channels play a vital role in helping fungal pathogens like Candida albicans adapt to hostile environments within the human body, including during infection. Among these, two-pore domain, outwardly rectifying K+ (TOK) channels, unique to fungi, have remained insufficiently characterized, despite evidence that they support processes in fungi, such as ion homeostasis, growth, and virulence, highlighting their potential as antifungal targets. Here, we present the cryo-EM structure of C. albicans TOK1 (CaTOK), the first resolved structure of a TOK channel and of any fungal K+ channel. CaTOK reveals an eight-transmembrane helical fold unlike any other K+ channel structure determined to date, including a domain formed by helices S1-S4 with unexpected structural homology to channel auxiliary subunits critical for human neuronal signaling. Additionally, a unique cytosolic C-terminal domain interfaces with pore-lining helices, suggesting a role in channel regulation. These findings uncover previously unrecognized structural elements that broaden our understanding of K+ channel diversity and regulation and provide initial clues into the structural basis for the unique functional attributes of the TOK family.

Details

Title: Subtitle: BPS2026 – Molecular architecture of the fungal-specific potassium channel TOK1
Creators: Brice Durocher - University of Iowa
Rían W. Manville - University of California, Irvine
Rui Yan - Janelia Research Campus
Zhiheng Yu - Janelia Research Campus
Geoffrey W. Abbott - University of California, Irvine
Alexandria N. Miller - University of Iowa
Resource Type: Abstract
Publication Details: Biophysical journal, Vol.125(4 Supplement 1), p.20
DOI: 10.1016/j.bpj.2025.11.316
ISSN: 0006-3495
Publisher: Elsevier
Language: English
Date published: 02/2026
Academic Unit: Molecular Physiology and Biophysics
Record Identifier: 9985141958102771

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