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- PDB-7rjc: Complex III2 from Candida albicans, inhibitor free, Rieske head d... -

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Basic information

Entry
Database: PDB / ID: 7rjc
TitleComplex III2 from Candida albicans, inhibitor free, Rieske head domain in intermediate position
Components
  • (Cytochrome b-c1 complex subunit ...) x 3
  • (Ubiquinol--cytochrome-c reductase ...) x 5
  • Cytochrome b
KeywordsMEMBRANE PROTEIN / Candida albicans / mitochondrial complex III2 / indazole-derivative inhibitor / Rieske head domain
Function / homology
Function and homology information


regulation of filamentous growth / matrix side of mitochondrial inner membrane / protein processing involved in protein targeting to mitochondrion / mitochondrial respiratory chain complex III assembly / mitochondrial respiratory chain complex III / quinol-cytochrome-c reductase / ubiquinol-cytochrome-c reductase activity / mitochondrial electron transport, ubiquinol to cytochrome c / mitochondrial crista / heterochromatin ...regulation of filamentous growth / matrix side of mitochondrial inner membrane / protein processing involved in protein targeting to mitochondrion / mitochondrial respiratory chain complex III assembly / mitochondrial respiratory chain complex III / quinol-cytochrome-c reductase / ubiquinol-cytochrome-c reductase activity / mitochondrial electron transport, ubiquinol to cytochrome c / mitochondrial crista / heterochromatin / aerobic respiration / 2 iron, 2 sulfur cluster binding / metalloendopeptidase activity / electron transfer activity / oxidoreductase activity / heme binding / mitochondrion / membrane / metal ion binding / plasma membrane
Similarity search - Function
Cytochrome b-c1 complex, subunit 6 / Cytochrome b-c1 complex subunit 8 / UcrQ family / Cytochrome bc1 complex subunit Rieske, transmembrane domain superfamily / Cytochrome b-c1 complex subunit 7 / Cytochrome b-c1 complex subunit 7 superfamily / Ubiquinol-cytochrome C reductase complex 14kD subunit / Cytochrome b-c1 complex subunit 9 / Cytochrome b-c1 complex subunit 8 superfamily / Cytochrome b-c1 complex subunit 9 superfamily ...Cytochrome b-c1 complex, subunit 6 / Cytochrome b-c1 complex subunit 8 / UcrQ family / Cytochrome bc1 complex subunit Rieske, transmembrane domain superfamily / Cytochrome b-c1 complex subunit 7 / Cytochrome b-c1 complex subunit 7 superfamily / Ubiquinol-cytochrome C reductase complex 14kD subunit / Cytochrome b-c1 complex subunit 9 / Cytochrome b-c1 complex subunit 8 superfamily / Cytochrome b-c1 complex subunit 9 superfamily / Ubiquinol-cytochrome C reductase, UQCRX/QCR9 like / Cytochrome b-c1 complex subunit Rieske, transmembrane domain / Ubiquinol cytochrome reductase transmembrane region / Ubiquinol-cytochrome C reductase hinge domain / Ubiquinol-cytochrome C reductase hinge domain superfamily / Ubiquinol-cytochrome C reductase hinge protein / Cytochrome c1, transmembrane anchor, C-terminal / Cytochrome b / : / : / Ubiquinol-cytochrome c reductase, iron-sulphur subunit / Cytochrome c1 / Cytochrome C1 family / Cytochrome b/b6, C-terminal / Cytochrome b(C-terminal)/b6/petD / Cytochrome b/b6 C-terminal region profile. / Cytochrome b/b6, C-terminal domain superfamily / Cytochrome b/b6/petB / Rieske iron-sulphur protein, C-terminal / Cytochrome b/b6, N-terminal / Cytochrome b/b6-like domain superfamily / Cytochrome b/b6 N-terminal region profile. / Di-haem cytochrome, transmembrane / Rieske iron-sulphur protein / Peptidase M16, C-terminal / Peptidase M16 inactive domain / Peptidase M16, N-terminal / Insulinase (Peptidase family M16) / Metalloenzyme, LuxS/M16 peptidase-like / Rieske [2Fe-2S] iron-sulphur domain / Rieske [2Fe-2S] domain / Rieske [2Fe-2S] iron-sulfur domain profile. / Rieske [2Fe-2S] iron-sulphur domain superfamily / Cytochrome c family profile. / Cytochrome c-like domain / Cytochrome c-like domain superfamily
Similarity search - Domain/homology
FE2/S2 (INORGANIC) CLUSTER / HEME C / PROTOPORPHYRIN IX CONTAINING FE / UBIQUINONE-10 / Cytochrome b-c1 complex subunit 8, mitochondrial / Cytochrome b-c1 complex catalytic subunit, mitochondrial / Cytochrome b-c1 complex subunit 6, mitochondrial / Cytochrome b-c1 complex subunit Rieske, mitochondrial / Cytochrome b-c1 complex subunit 9, mitochondrial / Cytochrome b-c1 complex reductase subunit, mitochondrial ...FE2/S2 (INORGANIC) CLUSTER / HEME C / PROTOPORPHYRIN IX CONTAINING FE / UBIQUINONE-10 / Cytochrome b-c1 complex subunit 8, mitochondrial / Cytochrome b-c1 complex catalytic subunit, mitochondrial / Cytochrome b-c1 complex subunit 6, mitochondrial / Cytochrome b-c1 complex subunit Rieske, mitochondrial / Cytochrome b-c1 complex subunit 9, mitochondrial / Cytochrome b-c1 complex reductase subunit, mitochondrial / Cytochrome b / Cytochrome b-c1 complex subunit 2, mitochondrial / Cytochrome b-c1 complex subunit 7, mitochondrial
Similarity search - Component
Biological speciesCandida albicans (yeast)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsDi Trani, J.M. / Rubinstein, J.L.
Funding support Canada, Sweden, 5items
OrganizationGrant numberCountry
Canadian Institutes of Health Research (CIHR)PJT162186 Canada
Canadian Institutes of Health Research (CIHR)FDN154288 Canada
Knut and Alice Wallenberg Foundation2019.0043 Sweden
Swedish Research Council2018-04619 Sweden
Canada Research Chairs Canada
CitationJournal: Structure / Year: 2022
Title: Rieske head domain dynamics and indazole-derivative inhibition of Candida albicans complex III.
Authors: Justin M Di Trani / Zhongle Liu / Luke Whitesell / Peter Brzezinski / Leah E Cowen / John L Rubinstein /
Abstract: Electron 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.
History
DepositionJul 20, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 15, 2021Provider: repository / Type: Initial release
Revision 1.1Sep 29, 2021Group: Database references / Category: citation / citation_author
Item: _citation.journal_abbrev / _citation.journal_id_ISSN ..._citation.journal_abbrev / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name
Revision 1.2Jan 19, 2022Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.year

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Structure visualization

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Assembly

Deposited unit
A: Ubiquinol--cytochrome-c reductase subunit
K: Cytochrome b
D: Ubiquinol--cytochrome-c reductase catalytic subunit
G: Cytochrome b-c1 complex subunit 7
F: Ubiquinol--cytochrome-c reductase subunit 8
H: Ubiquinol--cytochrome-c reductase subunit 6
I: Ubiquinol--cytochrome-c reductase subunit 9
B: Cytochrome b-c1 complex subunit 2, mitochondrial
M: Cytochrome b-c1 complex subunit Rieske, mitochondrial
E: Cytochrome b-c1 complex subunit Rieske, mitochondrial
hetero molecules


Theoretical massNumber of molelcules
Total (without water)259,96516
Polymers256,21110
Non-polymers3,7546
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area34600 Å2
ΔGint-315 kcal/mol
Surface area76200 Å2

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Components

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Ubiquinol--cytochrome-c reductase ... , 5 types, 5 molecules ADFHI

#1: Protein Ubiquinol--cytochrome-c reductase subunit


Mass: 48004.805 Da / Num. of mol.: 1 / Source method: isolated from a natural source
Source: (natural) Candida albicans (strain SC5314 / ATCC MYA-2876) (yeast)
Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PP59
#3: Protein Ubiquinol--cytochrome-c reductase catalytic subunit


Mass: 32261.389 Da / Num. of mol.: 1 / Source method: isolated from a natural source
Source: (natural) Candida albicans (strain SC5314 / ATCC MYA-2876) (yeast)
Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PHA3
#5: Protein Ubiquinol--cytochrome-c reductase subunit 8


Mass: 11125.672 Da / Num. of mol.: 1 / Source method: isolated from a natural source
Source: (natural) Candida albicans (strain SC5314 / ATCC MYA-2876) (yeast)
Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PHA2
#6: Protein Ubiquinol--cytochrome-c reductase subunit 6


Mass: 16042.014 Da / Num. of mol.: 1 / Source method: isolated from a natural source
Source: (natural) Candida albicans (strain SC5314 / ATCC MYA-2876) (yeast)
Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PJT8
#7: Protein/peptide Ubiquinol--cytochrome-c reductase subunit 9


Mass: 4538.231 Da / Num. of mol.: 1 / Source method: isolated from a natural source
Source: (natural) Candida albicans (strain SC5314 / ATCC MYA-2876) (yeast)
Strain: SC5314 / ATCC MYA-2876 / References: UniProt: A0A1D8PLP3

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Protein , 1 types, 1 molecules K

#2: Protein Cytochrome b / / Complex III subunit 3 / Complex III subunit III / Cytochrome b-c1 complex subunit 3 / Ubiquinol- ...Complex III subunit 3 / Complex III subunit III / Cytochrome b-c1 complex subunit 3 / Ubiquinol-cytochrome-c reductase complex cytochrome b subunit


Mass: 43738.457 Da / Num. of mol.: 1 / Source method: isolated from a natural source
Source: (natural) Candida albicans (strain SC5314 / ATCC MYA-2876) (yeast)
Strain: SC5314 / ATCC MYA-2876 / References: UniProt: P0C8L0

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Cytochrome b-c1 complex subunit ... , 3 types, 4 molecules GBME

#4: Protein Cytochrome b-c1 complex subunit 7


Mass: 14440.710 Da / Num. of mol.: 1 / Source method: isolated from a natural source
Source: (natural) Candida albicans (strain SC5314 / ATCC MYA-2876) (yeast)
Strain: SC5314 / ATCC MYA-2876 / References: UniProt: Q5ABS1
#8: Protein Cytochrome b-c1 complex subunit 2, mitochondrial / Complex III subunit 2 / Core protein II / Cytoplasmic antigenic protein 5 / Ubiquinol-cytochrome-c ...Complex III subunit 2 / Core protein II / Cytoplasmic antigenic protein 5 / Ubiquinol-cytochrome-c reductase complex core protein 2


Mass: 39593.352 Da / Num. of mol.: 1 / Source method: isolated from a natural source
Source: (natural) Candida albicans (strain SC5314 / ATCC MYA-2876) (yeast)
Strain: SC5314 / ATCC MYA-2876 / References: UniProt: P83782
#9: Protein Cytochrome b-c1 complex subunit Rieske, mitochondrial


Mass: 23233.385 Da / Num. of mol.: 2 / Source method: isolated from a natural source
Source: (natural) Candida albicans (strain SC5314 / ATCC MYA-2876) (yeast)
Strain: SC5314 / ATCC MYA-2876
References: UniProt: A0A1D8PJX3, quinol-cytochrome-c reductase

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Non-polymers , 4 types, 6 molecules

#10: Chemical ChemComp-HEM / PROTOPORPHYRIN IX CONTAINING FE / HEME / Heme B


Mass: 616.487 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C34H32FeN4O4
#11: Chemical ChemComp-U10 / UBIQUINONE-10 / Coenzyme Q10 / Coenzyme Q10


Mass: 863.343 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C59H90O4
#12: Chemical ChemComp-HEC / HEME C / Heme C


Mass: 618.503 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C34H34FeN4O4
#13: Chemical ChemComp-FES / FE2/S2 (INORGANIC) CLUSTER / Iron–sulfur cluster


Mass: 175.820 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Fe2S2

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Details

Has ligand of interestN

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Respiratory complex III2 from Candida albicans / Type: COMPLEX / Entity ID: #1-#9 / Source: NATURAL
Source (natural)Organism: Candida albicans SC5314 (yeast)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE-PROPANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy
Image recordingElectron dose: 42 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 58556 / Symmetry type: POINT

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