The 2.8-Å structure of rat liver F1-ATPase:: Configuration of a critical intermediate in ATP synthesis/hydrolysis

During mitochondrial ATP synthesis, F-1-ATPase-the portion of the;ITP 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-Angstrom resolution in the presence of physiological concentrations of nucleotides, all three beta 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.