Molecular mechanisms of rotational catalysis in the F0F1 ATP synthase

Rotation of the F0F1 ATP synthase gamma subunit drives each of the three ca talytic sites through their reaction pathways. The enzyme completes three c ycles and synthesizes or hydrolyzes three ATP for each 360 degrees rotation of the gamma subunit. Mutagenesis studies have yielded considerable inform ation on the roles of interactions between the rotor gamma subunit and the catalytic beta subunits. Amino acid substitutions, such as replacement of t he conserved gamma Met-23 by Lys, cause altered interactions between gamma and beta subunits that have dramatic effects on the transition state of the steady state ATP synthesis and hydrolysis reactions. The mutations also pe rturb transmission of specific conformational information between subunits which is important for efficient conversion of energy between rotation and catalysis, and render the coupling between catalysis and transport ineffici ent. Amino acid replacements in the transport domain also affect the steady state catalytic transition state indicating that rotation is involved in c oupling to transport. (C) 2000 Elsevier Science B.V. All rights reserved.