Structure of ATP synthase under strain during catalysis

ATP synthases are macromolecular machines consisting of an ATP-hydrolysis-driven F-1 motor and a proton-translocation-driven F-O motor. The F-1 and F-O motors oppose each other's action on a shared rotor subcomplex and are held stationary relative to each other by a peripheral stalk. Structures of resting mitochondrial ATP synthases revealed a left-handed curvature of the peripheral stalk even though rotation of the rotor, driven by either ATP hydrolysis in F-1 or proton translocation through F-O, would apply a right-handed bending force to the stalk. We used cryoEM to image yeast mitochondrial ATP synthase under strain during ATP-hydrolysis-driven rotary catalysis, revealing a large deformation of the peripheral stalk. The structures show how the peripheral stalk opposes the bending force and suggests that during ATP synthesis proton translocation causes accumulation of strain in the stalk, which relaxes by driving the relative rotation of the rotor through six sub-steps within F-1, leading to catalysis. CryoEM of mitochondrial ATP synthase frozen during rotary catalysis reveals dramatic conformational changes in the peripheral stalk subcomplex, which enable the enzyme's efficient synthesis of ATP.

Automated summary

ATP synthases are composed of F-1 and F-O motors, which are held together by a peripheral stalk. The peripheral stalk can resist the bending force caused by the rotation of the rotor during ATP hydrolysis or proton translocation. CryoEM imaging of yeast mitochondrial ATP synthase during ATP-hydrolysis-driven rotary catalysis reveals a large deformation of the peripheral stalk. This deformation is caused by the accumulation of strain in the stalk due to proton translocation, which drives the relative rotation of the rotor and enables efficient synthesis of ATP.