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Structure paper

TitleStructures of Respiratory Supercomplex I+III Reveal Functional and Conformational Crosstalk.
Journal, issue, pagesMol Cell, Vol. 75, Issue 6, Page 1131-11146.e6, Year 2019
Publish dateSep 19, 2019
AuthorsJames A Letts / Karol Fiedorczuk / Gianluca Degliesposti / Mark Skehel / Leonid A Sazanov /
PubMed AbstractThe mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We ...The mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We demonstrate that CoQ trapping in the isolated SC I+III limits complex (C)I turnover, arguing against channeling. The SC structure, resolved at up to 3.8 Å in four distinct states, suggests that CoQ oxidation may be rate limiting because of unequal access of CoQ to the active sites of CIII. CI shows a transition between "closed" and "open" conformations, accompanied by the striking rotation of a key transmembrane helix. Furthermore, the state of CI affects the conformational flexibility within CIII, demonstrating crosstalk between the enzymes. CoQ was identified at only three of the four binding sites in CIII, suggesting that interaction with CI disrupts CIII symmetry in a functionally relevant manner. Together, these observations indicate a more nuanced functional role for the SCs.
External linksMol Cell / PubMed:31492636 / PubMed Central
MethodsEM (single particle)
Resolution3.8 - 7.5 Å
Structure data

4479

6q9b

EMDB-4479, PDB-6q9b:
CI Membrane Arm focused refinement from Ovine respiratory SC I+III2
Method: EM (single particle) / Resolution: 3.9 Å

4480

6q9d

EMDB-4480, PDB-6q9d:
CI Peripheral Arm focused refinement from Ovine respiratory SC I+III2
Method: EM (single particle) / Resolution: 3.8 Å

4481

6q9e

EMDB-4481, PDB-6q9e:
Complex III2 focused refinement from Ovine respiratory supercomplex I+III2
Method: EM (single particle) / Resolution: 3.9 Å

4482

6qa9

EMDB-4482, PDB-6qa9:
Isolated complex I class refinement from Ovine respiratory supercomplex I+III2
Method: EM (single particle) / Resolution: 4.1 Å

4493

6qbx

EMDB-4493, PDB-6qbx:
Ovine respiratory supercomplex I+III2 closed class.
Method: EM (single particle) / Resolution: 4.2 Å

4494

6qc2

EMDB-4494, PDB-6qc2:
Ovine respiratory supercomplex I+III2 open class 2
Method: EM (single particle) / Resolution: 4.2 Å

4495

6qc3

EMDB-4495, PDB-6qc3:
Ovine respiratory supercomplex I+III2 open class 1
Method: EM (single particle) / Resolution: 4.2 Å

4496

6qc4

EMDB-4496, PDB-6qc4:
Ovine respiratory supercomplex I+III2 open class 3
Method: EM (single particle) / Resolution: 4.6 Å

4497

6qc5

EMDB-4497, PDB-6qc5:
Ovine respiratory complex I FRC closed class 1
Method: EM (single particle) / Resolution: 4.3 Å

4498

6qc6

EMDB-4498, PDB-6qc6:
Ovine respiratory complex I FRC open class 1
Method: EM (single particle) / Resolution: 4.1 Å

4499

6qc7

EMDB-4499, PDB-6qc7:
Ovine respiratory complex I FRC open class 3
Method: EM (single particle) / Resolution: 4.4 Å

4500

6qc8

EMDB-4500, PDB-6qc8:
Ovine respiratory complex I FRC open class 2
Method: EM (single particle) / Resolution: 4.2 Å

4501

6qc9

EMDB-4501, PDB-6qc9:
Ovine respiratory complex I FRC open class 4
Method: EM (single particle) / Resolution: 5.7 Å

4502

6qca

EMDB-4502, PDB-6qca:
Ovine respiratory complex I FRC open class 5
Method: EM (single particle) / Resolution: 6.2 Å

4505

6qcf

EMDB-4505, PDB-6qcf:
Ovine respiratory complex I FRC open class 6
Method: EM (single particle) / Resolution: 6.5 Å

EMDB-4506:
Ovine respiratory complex I FRC poor closed class
Method: EM (single particle) / Resolution: 7.0 Å

EMDB-4507:
Ovine respiratory complex I FRC poor open class
Method: EM (single particle) / Resolution: 7.5 Å

Chemicals

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

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM / Cardiolipin

ChemComp-PC1:
1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE / phospholipid*YM / Phosphatidylcholine

ChemComp-ZMP:
S-[2-({N-[(2S)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alanyl}amino)ethyl] tetradecanethioate

ChemComp-SF4:
IRON/SULFUR CLUSTER / Iron–sulfur cluster

ChemComp-FMN:
FLAVIN MONONUCLEOTIDE / Flavin mononucleotide

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

ChemComp-ZN:
Unknown entry

ChemComp-NDP:
NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / Nicotinamide adenine dinucleotide phosphate

ChemComp-HEM:
PROTOPORPHYRIN IX CONTAINING FE / Heme B

ChemComp-U10:
UBIQUINONE-10 / Coenzyme Q10

ChemComp-HEC:
HEME C / Heme C

Source
  • ovis aries (sheep)
  • Sheep (sheep)
KeywordsELECTRON TRANSPORT / complex I / membrane arm / cellular respiration / mitochondria / peripheral arm / complex III / supercomplex

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