9w2s | pdb_00009w2s
Cryo-EM structure of FoF1-ATPase monomer state 3 on the bovine heart submitochondrial particles (FoF1-2)
Structural highlights
FunctionATPB_BOVIN Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F(1). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits. Publication Abstract from PubMedUnderstanding the functional mechanisms of membrane protein complexes requires structural analysis within their native membrane environment. Here, we applied cryo-electron microscopy to determine the structures of F(o)F(1) ATP synthase and respiratory supercomplexes (SCs) on sub-mitochondrial particles (SMPs) isolated from bovine heart mitochondria. Most F(o)F(1) complexes were observed as dimers stabilized by the regulatory factor IF(1), and a tetrameric assembly comprising two F(o)F(1)-IF(1) dimers arranged linearly was also identified. This finding indicates that the tetrameric units of F(o)F(1) are present in the mitochondrial inner membrane and contribute to shaping cristae tips in mammalian mitochondria. F(o) domain maps resolve the e-subunit- c(8)-ring interface and show no discrete density for a tightly bound lipid within the c(8)-ring. In addition to the previously reported SCs compositions CI(1)CIII(2)CIV(1) and CI(1)CIII(2)CIV(2), our analysis identified an additional assembly with the composition CI(1)CIII(2)CIV(3), as well as a CI(2)CIII(2)CIV(6) mega-complex. This approach enables rapid structural determination of F(o)F(1) ATP synthase and SCs from minimal membrane fractions, providing a foundation for elucidating the molecular basis of metabolic disorders and mitochondrial diseases at the level of higher-order architecture. Structures of respiratory supercomplexes and ATP synthase oligomers in mammalian mitochondrial inner membrane.,Nakano A, Masuya T, Akisada S, Ishikawa-Fukuda M, Mitsuoka K, Miyoshi H, Murai M, Yokoyama K Nat Commun. 2026 Mar 17. doi: 10.1038/s41467-026-70578-x. PMID:41844608[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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