Directed proton transfer from Fo to F1 extends the multifaceted proton functions in ATP synthase

• Published in: Biophysical reviews 2023-10, Vol.15 (5), p.859-873
• Main Authors: Nesterov, Semen V., Yaguzhinsky, Lev S.
• Format: Article
• Language: English
• Subjects: Acidification; Alkalizing; Amino acids; ATP synthase; Biochemistry; Biological and Medical Physics; Biological Techniques; Biomedical and Life Sciences; Biophysics; Cell Biology; Chemical synthesis; Chloroplasts; Electrochemical potential; Energy charge; Energy storage; Enzymatic activity; Enzyme activity; Enzymes; Life Sciences; Membrane Biology; Molecular machines; Nanotechnology; Phosphorylation; Protonation; Protons; Review; Rotation; Stroma
• ISSN: 1867-2450; 1867-2469
• DOI: 10.1007/s12551-023-01132-y

The role of protons in ATP synthase is typically considered to be energy storage in the form of an electrochemical potential, as well as an operating element proving rotation. However, this review emphasizes that protons also act as activators of conformational changes in F 1 and as direct participants in phosphorylation reaction. The protons transferred through F o do not immediately leave to the bulk aqueous phase, but instead provide for the formation of a pH gradient between acidifying F o and alkalizing F 1 . It facilitates a directed inter-subunit proton transfer to F 1 , where they are used in the ATP synthesis reaction. This ensures that the enzyme activity is not limited by a lack of protons in the alkaline mitochondrial matrix or chloroplast stroma. Up to one hundred protons bind to the carboxyl groups of the F 1 subunit, altering the electrical interactions between the amino acids of the enzyme. This removes the inhibition of ATP synthase caused by the electrostatic attraction of charged amino acids of the stator and rotor and also makes the enzyme more prone to conformational changes. Protonation occurs during ATP synthesis initiation and during phosphorylation, while deprotonation blocks the rotation inhibiting both synthesis and hydrolysis. Thus, protons participate in the functioning of all main components of ATP synthase molecular machine making it effectively a proton-driven electric machine. The review highlights the key role of protons as a coupling factor in ATP synthase with multifaceted functions, including charge and energy transport, torque generation, facilitation of conformational changes, and participation in the ATP synthesis reaction.