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Structure paper

TitleCryo-EM structure of bixafen-bound S. cerevisiae complex II unravels SDHI specificity against pathogenic fungi.
Journal, issue, pagesCommun Biol, Year 2026
Publish dateJan 28, 2026
AuthorsNikos Pinotsis / Claudia Burn-Leefe / Sarah Jones / Shu Chen / Natalya Lukoyanova / Brigitte Meunier / Edward A Berry / Amandine Maréchal /
PubMed AbstractRespiratory 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 ...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.
External linksCommun Biol / PubMed:41606097
MethodsEM (single particle)
Resolution3.0 - 3.15 Å
Structure data

53029

9qdl

EMDB-53029, PDB-9qdl:
CRYO-EM STRUCTURE OF THE YEAST RESPIRATORY COMPLEX II
Method: EM (single particle) / Resolution: 3.15 Å

53030

9qdm

EMDB-53030, PDB-9qdm:
CRYO-EM STRUCTURE OF THE YEAST RESPIRATORY COMPLEX II WITH THE INHIBITOR BIXAFEN
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-FAD:
FLAVIN-ADENINE DINUCLEOTIDE / FAD*YM

ChemComp-K:
Unknown entry

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER

ChemComp-SF4:
IRON/SULFUR CLUSTER

ChemComp-F3S:
FE3-S4 CLUSTER

PDB-1j2j:
Crystal structure of GGA1 GAT N-terminal region in complex with ARF1 GTP form

ChemComp-3PE:
1,2-Distearoyl-sn-glycerophosphoethanolamine / phospholipid*YM

ChemComp-7PO:
hexacosanoic acid

ChemComp-HOH:
WATER

PDB-1i6x:
STRUCTURE OF A STAR MUTANT CRP-CAMP AT 2.2 A

Source
  • saccharomyces cerevisiae (brewer's yeast)
  • saccharomyces cerevisiae w303 (yeast)
KeywordsOXIDOREDUCTASE / COMPLEX II / MEMBRANE PROTEIN / UBIQUINONE-1 / OXIDOREDUCTASE INHIBITOR COMPLEX / BIXAFEN

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