The Frasch Lab          


Induction Mechanism Hypothesis

    The binding and hydrolysis of ATP drives rotation of gamma subunit in the opposite direction from that during ATP synthesis.   Our results suggest that rotation of the g subunit is driven by an induction mechanism during ATP hydrolysis.  In this mechanism, MgATP binding to the empty catalytic site causes the beta subunit  catch loop to exchange the  hydrogen bonds and salt bridges it makes to the g subunit for those on the adjacent a subunit.  We hypothesize that charged and polar residues on both the  g and  the (ab)3 ring are positioned so that  the resulting changes in Coulombic potential drives the formation of new salt bridges and hydrogen bonds between the g and  the (ab)3 ring which in turn drives the rotation of the g subunit.  If the bonding pairs are staggered, then each bond will contribute to the torque for several degrees of rotation in succession.

For additional information concerning this hypothesis visit the simulations page.

Details of our recent evidence of the participation of  g Subunit N-Terminus Residues gK9 and gS12 with  bD372 are described below (Lowry and Frasch (2005) Biochemistry, 44; 7275-7281).


 Interactions between bD372 and g Subunit N-Terminus Residues gK9 and gS12 are Important to Catalytic Activity Catalyzed by E. Coli F1Fo-ATP Synthase†.

Download PDF from Biochemistry here

David S. Lowry and Wayne D. Frasch*

Center for the Study of Early Events in Photosynthesis

School of Life Sciences, Arizona State University, P.O. Box 874501, Tempe, AZ



Substitution of E. Coli F1Fo ATP synthase residues bD372 or gS12 with groups that are unable to form a hydrogen bond at this location decreased ATP synthase-dependent cell growth by two orders of magnitude, eliminated the ability of F1Fo to catalyze ATPase-dependent proton pumping in inverted E. coli membranes, caused a 15-20% decrease in the coupling efficiency of the membranes as measured by the extent of succinate-dependent acridine orange fluorescence quenching, but increased soluble F1-ATPase activity by about 10%. Substitution of gK9 to eliminate the ability to form a salt bridge with bD372 decreased soluble F1-ATPase activity and ATPase-driven proton pumping by two fold, but had no effect on the proton gradient induced by addition of succinate. Mutations to eliminate the potential to form intersubunit hydrogen bonds and salt bridges between other less highly conserved residues on the g subunit N-terminus and the b subunits had little effect on ATPase or ATP synthase activities. These results suggest that the bD372-gK9 salt bridge contributes significantly to the rate-limiting step in ATP hydrolysis of soluble F1 while the bD372-gS12 hydrogen-bond may serve as a component of an escapement mechanism for ATP synthesis in which abg intersubunit interactions provide a means to make substrate binding a prerequisite of proton gradient-driven g subunit rotation.


Last updated 2/20/2006

Frasch Lab

Arizona State University