ATP Synthesis, Qualitatively: Summary of July 17, 2012 Meeting

We discussed both the forward and reverse mechanisms of the F1F0 ATP synthase – i.e., both ATP synthesis and generation of rotary motion from ATP hydrolysis although limited to the F1 domain.  (Previously, Michael Grabe led our discussion of the F0 domain.)  Our discussion was based on the schematic model depicted in Berg’s textbook (http://www.ncbi.nlm.nih.gov/books/NBK22388/figure/A2538/).  While the schematic did provide a lot of qualitative insight, I think most of us felt unsatisfied with the attempt to understand a machine without at least a semi-quantitative basis.  Specifically, we know there are thermodynamically constrained relations among the various rates (for catalysis, binding, and conformational change) that would provide a much more concrete picture.  We will attempt to pursue this approach next time.

Some questions raised that we would like to address:

• What is the importance of the three-fold symmetry?  Would two sub-units be enough?  An initial answer is that only with three subunits can the directionality be ensured in the hydrolysis process.
• What is the minimal kinetic model that can explain ATP synthesis using mechanical force?  Are two subunits sufficient?
• What is the minimal kinetic model need for rotary motion?
• What insights can thermodynamically consistent kinetic models provide?