Cryo-EM structure of bixafen-bound S. cerevisiae complex II unravels SDHI specificity against pathogenic fungi
Abstract
Respiratory complex II (CII), or succinate dehydrogenase, couples succinate oxidation in the Krebs cycle with electron transfer to the respiratory chain. Owing to this pivotal role, CII inhibitors are widely used fungicides globally; however, their development has largely proceeded without structural insights from fungal targets. Here, we report cryo-electron microscopy structures of the 128 kDa mitochondrial CII from Saccharomyces cerevisiae in two states: active, with endogenous ubiquinone-6 bound (3.15 Å), and inhibited with the fungicide bixafen (3.00 Å). Although closely related to the mammalian type C enzyme, our structures show that the yeast CII has lost the canonical heme cofactor. They also reveal how clade-specific sequence extensions of the membrane subunits Sdh3 and Sdh4 - conserved in pathogenic fungi - uniquely contribute to complex stability and fungicide binding. Our findings provide a foundation for rational design of next-generation CII inhibitors and combatting resistance, in both agriculture and human health.
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BibTeX
@article{pinotsis2026cryoem,
title = {{Cryo-EM structure of bixafen-bound S. cerevisiae complex II unravels SDHI specificity against pathogenic fungi}},
author = {Nikos Pinotsis and Claudia Burn-Leefe and Sarah Jones and Shu Chen and Natalya Lukoyanova and Brigitte Meunier and Edward A Berry and Amandine Maréchal},
journal = {Communications Biology},
year = {2026},
month = sep,
doi = {10.1038/s42003-026-09617-8},
url = {https://hal.science/hal-05760677v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Cryo-EM structure of bixafen-bound S. cerevisiae complex II unravels SDHI specificity against pathogenic fungi
AU - Nikos Pinotsis
AU - Claudia Burn-Leefe
AU - Sarah Jones
AU - Shu Chen
AU - Natalya Lukoyanova
AU - Brigitte Meunier
AU - Edward A Berry
AU - Amandine Maréchal
PY - 2026
DA - 2026/09/23
JO - Communications Biology
DO - 10.1038/s42003-026-09617-8
UR - https://hal.science/hal-05760677v1
AB - Respiratory complex II (CII), or succinate dehydrogenase, couples succinate oxidation in the Krebs cycle with electron transfer to the respiratory chain. Owing to this pivotal role, CII inhibitors are widely used fungicides globally; however, their development has largely proceeded without structural insights from fungal targets. Here, we report cryo-electron microscopy structures of the 128 kDa mitochondrial CII from Saccharomyces cerevisiae in two states: active, with endogenous ubiquinone-6 bound (3.15 Å), and inhibited with the fungicide bixafen (3.00 Å). Although closely related to the mammalian type C enzyme, our structures show that the yeast CII has lost the canonical heme cofactor. They also reveal how clade-specific sequence extensions of the membrane subunits Sdh3 and Sdh4 - conserved in pathogenic fungi - uniquely contribute to complex stability and fungicide binding. Our findings provide a foundation for rational design of next-generation CII inhibitors and combatting resistance, in both agriculture and human health.
SN - 2399-3642
ER -