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Structure paper

TitleRieske head domain dynamics and indazole-derivative inhibition of Candida albicans complex III.
Journal, issue, pagesStructure, Vol. 30, Issue 1, Page 129-138.e4, Year 2022
Publish dateJan 6, 2022
AuthorsJustin M Di Trani / Zhongle Liu / Luke Whitesell / Peter Brzezinski / Leah E Cowen / John L Rubinstein /
PubMed AbstractElectron transfer between respiratory complexes drives transmembrane proton translocation, which powers ATP synthesis and membrane transport. The homodimeric respiratory complex III (CIII) oxidizes ...Electron transfer between respiratory complexes drives transmembrane proton translocation, which powers ATP synthesis and membrane transport. The homodimeric respiratory complex III (CIII) oxidizes ubiquinol to ubiquinone, transferring electrons to cytochrome c and translocating protons through a mechanism known as the Q cycle. The Q cycle involves ubiquinol oxidation and ubiquinone reduction at two different sites within each CIII monomer, as well as movement of the head domain of the Rieske subunit. We determined structures of Candida albicans CIII by cryoelectron microscopy (cryo-EM), revealing endogenous ubiquinone and visualizing the continuum of Rieske head domain conformations. Analysis of these conformations does not indicate cooperativity in the Rieske head domain position or ligand binding in the two CIIIs of the CIII dimer. Cryo-EM with the indazole derivative Inz-5, which inhibits fungal CIII and is fungicidal when administered with fungistatic azole drugs, showed that Inz-5 inhibition alters the equilibrium of Rieske head domain positions.
External linksStructure / PubMed:34525326
MethodsEM (single particle)
Resolution3.0 - 3.3 Å
Structure data

24482

7rja

EMDB-24482, PDB-7rja:
Complex III2 from Candida albicans, inhibitor free
Method: EM (single particle) / Resolution: 3.0 Å

24483

7rjb

EMDB-24483, PDB-7rjb:
Complex III2 from Candida albicans, inhibitor free, Rieske head domain in b position
Method: EM (single particle) / Resolution: 3.2 Å

24484

7rjc

EMDB-24484, PDB-7rjc:
Complex III2 from Candida albicans, inhibitor free, Rieske head domain in intermediate position
Method: EM (single particle) / Resolution: 3.3 Å

24485

7rjd

EMDB-24485, PDB-7rjd:
Complex III2 from Candida albicans, inhibitor free, Rieske head domain in c position
Method: EM (single particle) / Resolution: 3.2 Å

24486

7rje

EMDB-24486, PDB-7rje:
Complex III2 from Candida albicans, Inz-5 bound
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-HEM:
PROTOPORPHYRIN IX CONTAINING FE / Heme B

ChemComp-U10:
UBIQUINONE-10 / Coenzyme Q10

ChemComp-HEC:
HEME C / Heme C

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER / Iron–sulfur cluster

ChemComp-ZL5:
3-[2-fluoro-5-(trifluoromethyl)phenyl]-7-methyl-1-[(2-methyl-2H-tetrazol-5-yl)methyl]-1H-indazole

Source
  • Candida albicans SC5314 (yeast)
  • Yeast (yeast)
  • candida albicans (strain sc5314 / atcc mya-2876) (yeast)
KeywordsMEMBRANE PROTEIN / Candida albicans / mitochondrial complex III2 / indazole-derivative inhibitor / Rieske head domain

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