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Title | Conformational ensemble of yeast ATP synthase at low pH reveals unique intermediates and plasticity in F-F coupling. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 31, Issue 4, Page 657-666, Year 2024 |
Publish date | Feb 5, 2024 |
Authors | Stuti Sharma / Min Luo / Hiral Patel / David M Mueller / Maofu Liao / |
PubMed Abstract | Mitochondrial adenosine triphosphate (ATP) synthase uses the proton gradient across the inner mitochondrial membrane to synthesize ATP. Structural and single molecule studies conducted mostly at ...Mitochondrial adenosine triphosphate (ATP) synthase uses the proton gradient across the inner mitochondrial membrane to synthesize ATP. Structural and single molecule studies conducted mostly at neutral or basic pH have provided details of the reaction mechanism of ATP synthesis. However, pH of the mitochondrial matrix is slightly acidic during hypoxia and pH-dependent conformational changes in the ATP synthase have been reported. Here we use single-particle cryo-EM to analyze the conformational ensemble of the yeast (Saccharomyces cerevisiae) ATP synthase at pH 6. Of the four conformations resolved in this study, three are reaction intermediates. In addition to canonical catalytic dwell and binding dwell structures, we identify two unique conformations with nearly identical positions of the central rotor but different catalytic site conformations. These structures provide new insights into the catalytic mechanism of the ATP synthase and highlight elastic coupling between the catalytic and proton translocating domains. |
External links | Nat Struct Mol Biol / PubMed:38316880 |
Methods | EM (single particle) |
Resolution | 2.7 - 4.5 Å |
Structure data | EMDB-28685: Yeast ATP synthase consensus map in conformation-0 at pH 6 EMDB-28687: Yeast ATP synthase F1-focused map in conformation-0 at pH 6 EMDB-28689: Yeast ATP synthase Fo-focused map in conformation-0 at pH 6 EMDB-28809: Yeast ATP synthase map in conformation-1 at pH 6 EMDB-28811: F1-focused map of yeast ATP synthase in conformation-1, at pH 6 EMDB-28814: Fo and central rotor focused map of yeast ATP synthase in conformation-1, at pH 6 EMDB-28835: Yeast ATP synthase map in conformation-2, at pH 6 EMDB-28836: F1-focused map of yeast ATP synthase in conformation-2, at pH 6 EMDB-28837: Fo and central rotor focused map of yeast ATP synthase in conformation-2, at pH 6 EMDB-29250, PDB-8fkj: EMDB-29251: Fo and central rotor focused map of yeast ATP Synthase in conformation-3, at pH 6 EMDB-29270: Yeast ATP Synthase map in presence of MgATP EMDB-29278: F1-focused map of yeast ATP Synthase in presence of MgATP |
Chemicals | ChemComp-ADP: ChemComp-MG: ChemComp-PO4: ChemComp-ATP: |
Source |
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Keywords | MEMBRANE PROTEIN / F-type ATP synthase / yeast / mitochondrial / F-type / ATP Synthase |