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Structure paper

TitleHigh-resolution cryo-EM structures of respiratory complex I: Mechanism, assembly, and disease.
Journal, issue, pagesSci Adv, Vol. 5, Issue 12, Page eaax9484, Year 2019
Publish dateDec 11, 2019
AuthorsKristian Parey / Outi Haapanen / Vivek Sharma / Harald Köfeler / Thomas Züllig / Simone Prinz / Karin Siegmund / Ilka Wittig / Deryck J Mills / Janet Vonck / Werner Kühlbrandt / Volker Zickermann /
PubMed AbstractRespiratory complex I is a redox-driven proton pump, accounting for a large part of the electrochemical gradient that powers mitochondrial adenosine triphosphate synthesis. Complex I dysfunction is ...Respiratory complex I is a redox-driven proton pump, accounting for a large part of the electrochemical gradient that powers mitochondrial adenosine triphosphate synthesis. Complex I dysfunction is associated with severe human diseases. Assembly of the one-megadalton complex I in the inner mitochondrial membrane requires assembly factors and chaperones. We have determined the structure of complex I from the aerobic yeast by electron cryo-microscopy at 3.2-Å resolution. A ubiquinone molecule was identified in the access path to the active site. The electron cryo-microscopy structure indicated an unusual lipid-protein arrangement at the junction of membrane and matrix arms that was confirmed by molecular simulations. The structure of a complex I mutant and an assembly intermediate provide detailed molecular insights into the cause of a hereditary complex I-linked disease and complex I assembly in the inner mitochondrial membrane.
External linksSci Adv / PubMed:31844670 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 4.04 Å
Structure data

4872

6rfq

EMDB-4872, PDB-6rfq:
Cryo-EM structure of a respiratory complex I assembly intermediate with NDUFAF2
Method: EM (single particle) / Resolution: 3.3 Å

4873

6rfr

EMDB-4873, PDB-6rfr:
Cryo-EM structure of respiratory complex I from Yarrowia lipolytica at 3.2 A resolution
Method: EM (single particle) / Resolution: 3.2 Å

4874

6rfs

EMDB-4874, PDB-6rfs:
Cryo-EM structure of a respiratory complex I mutant lacking NDUFS4
Method: EM (single particle) / Resolution: 4.04 Å

Chemicals

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

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

ChemComp-FMN:
FLAVIN MONONUCLEOTIDE / Flavin mononucleotide

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

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

ChemComp-LMN:
Lauryl Maltose Neopentyl Glycol / detergent*YM

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM / Cardiolipin

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

ChemComp-PLC:
DIUNDECYL PHOSPHATIDYL CHOLINE / phospholipid*YM

ChemComp-T7X:
Phosphatidylinositol / Phosphatidylinositol

ChemComp-CPL:
1-PALMITOYL-2-LINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / phospholipid*YM / Phosphatidylcholine

ChemComp-ZN:
Unknown entry

ChemComp-UQ9:
Ubiquinone-9

Source
  • yarrowia lipolytica (yeast)
  • Candida lipolytica (yeast)
KeywordsOXIDOREDUCTASE / Complex I / NADH dehydrogenase / Mitochondrion Proton pumping / Ubiquinone

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