| Autor: |
Marciniak A; Department of Physical Chemistry, Gdansk University of Technology, Narutowicza St 11/12, 80-233 Gdansk, Poland., Chodnicki P; Department of Physical Chemistry, Gdansk University of Technology, Narutowicza St 11/12, 80-233 Gdansk, Poland., Hossain KA; Department of Physical Chemistry, Gdansk University of Technology, Narutowicza St 11/12, 80-233 Gdansk, Poland., Slabonska J; Department of Physical Chemistry, Gdansk University of Technology, Narutowicza St 11/12, 80-233 Gdansk, Poland., Czub J; Department of Physical Chemistry, Gdansk University of Technology, Narutowicza St 11/12, 80-233 Gdansk, Poland.; BioTechMed Center, Gdansk University of Technology, Narutowicza St 11/12, 80-233, Gdansk, Poland. |
| Abstrakt: |
F o subcomplex of ATP synthase is a membrane-embedded rotary motor that converts proton motive force into mechanical energy. Despite a rapid increase in the number of high-resolution structures, the mechanism of tight coupling between proton transport and motion of the rotary c-ring remains elusive. Here, using extensive all-atom free energy simulations, we show how the motor's directionality naturally arises from the interplay between intraprotein interactions and energetics of protonation of the c-ring. Notably, our calculations reveal that the strictly conserved arginine in the a-subunit (R176) serves as a jack-of-all-trades: it dictates the direction of rotation, controls the protonation state of the proton-release site, and separates the two proton-access half-channels. Therefore, arginine is necessary to avoid slippage between the proton flux and the mechanical output and guarantees highly efficient energy conversion. We also provide mechanistic explanations for the reported defective mutations of R176, reconciling the structural information on the F o motor with previous functional and single-molecule data. |
