The 2.8-Å structure of rat liver F(1)-ATPase: Configuration of a critical intermediate in ATP synthesis/hydrolysis

During mitochondrial ATP synthesis, F(1)-ATPase—the portion of the ATP synthase that contains the catalytic and regulatory nucleotide binding sites—undergoes a series of concerted conformational changes that couple proton translocation to the synthesis of the high levels of ATP required for cellular function. In the structure of the rat liver F(1)-ATPase, determined to 2.8-Å resolution in the presence of physiological concentrations of nucleotides, all three β subunits contain bound nucleotide and adopt similar conformations. This structure provides the missing configuration of F(1) necessary to define all intermediates in the reaction pathway. Incorporation of this structure suggests a mechanism of ATP synthesis/hydrolysis in which configurations of the enzyme with three bound nucleotides play an essential role.