Meeting Summary - June 26, 2012

Stated Goals

Topic: More on energy transduction & use via molecular machines.  Michael Grabe will attend as a discussion leader.

Reading 

“Energy transduction in ATP synthase,” by Elston, Wang, and Oster.  Nature 391:510-513, 1998.  http://www.cnr.berkeley.edu/~goster/pdfs/FoMotor.pdf

And don't forget to keep on reading Franklin Harold's book. 

Meeting Summary - June 26, 2012 

I thought this was a very exciting meeting because, in previous meetings, we relied on cartoons and kinetic models, but now we explored a truly structural mechanism for ATP synthesis.

Michael Grabe led us through the Oster paper about the F1F0 ATP synthase, which primarily describes the transduction of a trans-membrane proton gradient into rotary motion via the F0 portion of the molecule.  The membrane-sited F0 contains rotor and stator domains.  The rotary motion is generated because Asp residues on the rotor permit or prohibit rotation depending on whether they are protonated.  (Protonation allows rotation because only charge-neutralized Asp's can exit the stator region, which covers only part of the rotor, and enter the hydrophobic membrane environment.)  The rotation is rectified and made uni-directional on average because of the much higher density of protons on the acid side of the membrane: the higher density encourages protonation of some sites over others.


The paper makes other points of interest: (1) The rotation is made quasi-mechanistic, with few backsteps, because a charged residue on the stator (Arg 210) greatly increases the barrier to rotation (in either direction).  (2) The qualitative picture just described is quantified using a Markov-state model which is simulated and apparently is consistent with experimental data.  Prof. Grabe provided a beautiful presentation of this material.

In the bigger picture, it must be understood how this rotary motion drives ATP synthesis in the F1 domain (an issue not addressed in the Oster paper).