Structure of the ATP synthase catalytic complex (F1) from Escherichia coli in an autoinhibited conformation

Abstract

ATP synthase functions as a rotary motor and its structure and function are conserved from bacteria to mitochondria and chloroplasts. The crystal structure of the ATP synthase catalytic complex (F1) from Escherichia coli in an auto-inhibited conformation reveals the structural basis for this inhibition, which occurs in ATP synthases of bacteria and chloroplasts, but not of mitochondria. ATP synthase is a membrane-bound rotary motor enzyme that is critical for cellular energy metabolism in all kingdoms of life. Despite conservation of its basic structure and function, autoinhibition by one of its rotary stalk subunits occurs in bacteria and chloroplasts but not in mitochondria. The crystal structure of the ATP synthase catalytic complex (F1) from Escherichia coli described here reveals the structural basis for this inhibition. The C-terminal domain of subunit ɛ adopts a heretofore unknown, highly extended conformation that inserts deeply into the central cavity of the enzyme and engages both rotor and stator subunits in extensive contacts that are incompatible with functional rotation. As a result, the three catalytic subunits are stabilized in a set of conformations and rotational positions distinct from previous F1 structures.