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III2IV respiratory supercomplex from Saccharomyces cerevisiae cardiolipin-lacking mutantIII2IV respiratory supercomplex from Saccharomyces cerevisiae cardiolipin-lacking mutant
Structural highlights
FunctionQCR1_YEAST Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain that generates an electrochemical potential coupled to ATP synthesis. The complex couples electron transfer from ubiquinol to cytochrome c. COR1 may mediate formation of the complex between cytochromes c and c1. Publication Abstract from PubMedCardiolipin 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 (IV(1)III(2)IV(1)) and a supercomplex (III(2)IV(1)) isolated from a cardiolipin-lacking Saccharomyces cerevisiae mutant at 3.2-A and 3.3-A resolution, respectively, and demonstrate that phosphatidylglycerol in III(2)IV(1) occupies similar positions as cardiolipin in IV(1)III(2)IV(1). Lipid-protein interactions within these complexes differ, which conceivably underlies the reduced level of IV(1)III(2)IV(1) and high levels of III(2)IV(1) and free III(2) 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. Structural insights into cardiolipin replacement by phosphatidylglycerol in a cardiolipin-lacking yeast respiratory supercomplex.,Hryc CF, Mallampalli VKPS, Bovshik EI, Azinas S, Fan G, Serysheva II, Sparagna GC, Baker ML, Mileykovskaya E, Dowhan W Nat Commun. 2023 May 15;14(1):2783. doi: 10.1038/s41467-023-38441-5. PMID:37188665[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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