Insights on the proton translocation pathways in FoF1-ATP synthase using molecular dynamics simulations

Proton translocation through the F-o fraction of FoF1-ATP synthase is one of the crucial processes in the catalytic cycle of the enzyme. However, the exact trace of protons movement has not been finally established yet because the location and structure of the half-channels are still the subject of investigation. We described the possible network of polar amino acids residues and water molecules that can favor the preferential proton pathway using molecular dynamics simulation of the membrane part of the E. coli ATP synthase embedded in the lipid bilayer and water environment. The inlet half-channel was a complex structure with two entrances in the form of aqueous lacunae and a highly conservative proton transfer chain near Asp61 of c-subunit including amino acids residues and three structural water molecules (W1-W3), while the outlet half-channel was just a water cavity through which a proton can easily move into the cytoplasm. Moreover, the side chains of Asn214 and Gln252 of a-subunit had the stable spatial positions (SP1-SP3). aAsn214 in position SP3 and aGln252 in SP1, SP2 were oriented towards cAsp61 and could presumably protonate it via W1. Herewith aAsn214 in SP1, SP2 was oriented to aHis245. Thus, the proton transfer chain is always unclosed, and switching between positions SP1/SP2 and SP3 of aAsn214 determines the time of proton transport and the movement in this region is the rate-limiting step. In addition, we found another rare position SP3, in which aGln252 is oriented to aAsn116 and aSer144, located outside of the main H+ route and being a dead end. The new findings would help to evaluate the whole process of the proton translocation through FoF1-ATP synthase.

Automated summary

This study describes the possible network of polar amino acids residues and water molecules that form the preferential proton pathway in the proton translocation through the F-o fraction of FoF1-ATP synthase. The findings contribute to a better understanding of the mechanism of proton transport.