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Title | Structural insights into cardiolipin replacement by phosphatidylglycerol in a cardiolipin-lacking yeast respiratory supercomplex. |
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Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 2783, Year 2023 |
Publish date | May 15, 2023 |
Authors | Corey 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 Abstract | Cardiolipin 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 links | Nat Commun / PubMed:37188665 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.2 - 3.3 Å |
Structure data | EMDB-27940, PDB-8e7s: EMDB-28011, PDB-8ec0: |
Chemicals | ChemComp-PEF: ChemComp-FES: ChemComp-CDL: ChemComp-PCF: ChemComp-CN5: ChemComp-HEM: ChemComp-UQ6: ChemComp-HEA: ChemComp-CU: ChemComp-CUA: ChemComp-PGT: |
Source |
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Keywords | OXIDOREDUCTASE / S.cerevisiae / respiratory supercomplex / cardiolipin / UQ6 / phosphatidylglycerol |