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TitleStructural insights into cardiolipin replacement by phosphatidylglycerol in a cardiolipin-lacking yeast respiratory supercomplex.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 2783, Year 2023
Publish dateMay 15, 2023
AuthorsCorey F Hryc / Venkata K P S Mallampalli / Evgeniy I Bovshik / Stavros Azinas / Guizhen Fan / Irina I Serysheva / Genevieve C Sparagna / Matthew L Baker / Eugenia Mileykovskaya / William Dowhan /
PubMed AbstractCardiolipin is a hallmark phospholipid of mitochondrial membranes. Despite established significance of cardiolipin in supporting respiratory supercomplex organization, a mechanistic understanding of ...Cardiolipin is a hallmark phospholipid of mitochondrial membranes. Despite established significance of cardiolipin in supporting respiratory supercomplex organization, a mechanistic understanding of this lipid-protein interaction is still lacking. To address the essential role of cardiolipin in supercomplex organization, we report cryo-EM structures of a wild type supercomplex (IVIIIIV) and a supercomplex (IIIIV) isolated from a cardiolipin-lacking Saccharomyces cerevisiae mutant at 3.2-Å and 3.3-Å resolution, respectively, and demonstrate that phosphatidylglycerol in IIIIV occupies similar positions as cardiolipin in IVIIIIV. Lipid-protein interactions within these complexes differ, which conceivably underlies the reduced level of IVIIIIV and high levels of IIIIV and free III and IV in mutant mitochondria. Here we show that anionic phospholipids interact with positive amino acids and appear to nucleate a phospholipid domain at the interface between the individual complexes, which dampen charge repulsion and further stabilize interaction, respectively, between individual complexes.
External linksNat Commun / PubMed:37188665 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 3.3 Å
Structure data

27940

8e7s

EMDB-27940, PDB-8e7s:
III2IV2 respiratory supercomplex from Saccharomyces cerevisiae with 4 bound UQ6
Method: EM (single particle) / Resolution: 3.2 Å

28011

8ec0

EMDB-28011, PDB-8ec0:
III2IV respiratory supercomplex from Saccharomyces cerevisiae cardiolipin-lacking mutant
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-PEF:
DI-PALMITOYL-3-SN-PHOSPHATIDYLETHANOLAMINE / phospholipid*YM / Phosphatidylethanolamine

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

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM / Cardiolipin

ChemComp-PCF:
1,2-DIACYL-SN-GLYCERO-3-PHOSHOCHOLINE / Dipalmitoylphosphatidylcholine

ChemComp-CN5:
(5S,11R)-5,8,11-trihydroxy-5,11-dioxido-17-oxo-4,6,10,12,16-pentaoxa-5,11-diphosphaoctadec-1-yl pentadecanoate / Cardiolipin

ChemComp-HEM:
PROTOPORPHYRIN IX CONTAINING FE / Heme B

ChemComp-UQ6:
5-(3,7,11,15,19,23-HEXAMETHYL-TETRACOSA-2,6,10,14,18,22-HEXAENYL)-2,3-DIMETHOXY-6-METHYL-BENZENE-1,4-DIOL

ChemComp-HEA:
HEME-A / Heme A

ChemComp-CU:
COPPER (II) ION / Copper

ChemComp-CUA:
DINUCLEAR COPPER ION

ChemComp-PGT:
(1S)-2-{[{[(2R)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL STEARATE / phospholipid*YM / Phosphatidylglycerol

Source
  • saccharomyces cerevisiae (brewer's yeast)
  • baker's yeast (brewer's yeast)
KeywordsOXIDOREDUCTASE / S.cerevisiae / respiratory supercomplex / cardiolipin / UQ6 / phosphatidylglycerol

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