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TitleInsights into complex I assembly: Function of NDUFAF1 and a link with cardiolipin remodeling.
Journal, issue, pagesSci Adv, Vol. 8, Issue 46, Page eadd3855, Year 2022
Publish dateNov 18, 2022
AuthorsJonathan Schiller / Eike Laube / Ilka Wittig / Werner Kühlbrandt / Janet Vonck / Volker Zickermann /
PubMed AbstractRespiratory complex I is a ~1-MDa proton pump in mitochondria. Its structure has been revealed in great detail, but the structural basis of its assembly, in humans involving at least 15 assembly ...Respiratory complex I is a ~1-MDa proton pump in mitochondria. Its structure has been revealed in great detail, but the structural basis of its assembly, in humans involving at least 15 assembly factors, is essentially unknown. We determined cryo-electron microscopy structures of assembly intermediates associated with assembly factor NDUFAF1 in a yeast model system. Subunits ND2 and NDUFC2 together with assembly factors NDUFAF1 and CIA84 form the nucleation point of the NDUFAF1-dependent assembly pathway. Unexpectedly, the cardiolipin remodeling enzyme tafazzin is an integral component of this core complex. In a later intermediate, all 12 subunits of the proximal proton pump module have assembled. NDUFAF1 locks the central ND3 subunit in an assembly-competent conformation, and major rearrangements of central subunits are required for complex I maturation.
External linksSci Adv / PubMed:36383672 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 3.2 Å
Structure data

14764

7zkp

EMDB-14764, PDB-7zkp:
Late assembly intermediate of the proximal proton pumping module of complex I with assembly factors NDUFAF1 and CIA84
Method: EM (single particle) / Resolution: 3.2 Å

14765

7zkq

EMDB-14765, PDB-7zkq:
Early Pp module assembly intermediate of complex I
Method: EM (single particle) / Resolution: 3.15 Å

EMDB-14766: Late Pp module assembly intermediate of complex I without assembly factors
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-14770: Late assembly intermediate of the proximal proton pumping module of complex I with assembly factor NDUFAF1
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM / Cardiolipin

ChemComp-PLC:
DIUNDECYL PHOSPHATIDYL CHOLINE / phospholipid*YM

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

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

ChemComp-T7X:
Phosphatidylinositol / Phosphatidylinositol

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

Source
  • yarrowia lipolytica (yeast)
KeywordsELECTRON TRANSPORT / assembly respiratory chain membrane protein mitochondria

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