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Center for Nonlinear Studies |
A transmembrane proton gradient is established in cells by proton pumping through membrane embedded proteins from the N-side of the membrane, with fewer protons, to the P-side, which has more protons. The proton gradient fuels the controlled transfer of ions and substrates across the membrane needed for cell signaling and metabolism and the production of ATP, the universal energy currency for biochemical reactions, by the F0/F1 ATPase. The energy to build the gradient comes from sunlight in photosynthesis or from energy liberated by redox chemistry such as in the reduction of oxygen in cytochrome c oxidase. The reactions start with long-range electron tunneling between cofactors embedded in the proteins. Proton transfers are then coupled to the electron transfer reactions (PCET). Proton pumping involves changes in the proton affinity of buried amino acids and active site ligands. A hydrogen bond pathway containing ionizable and polar residues and waters must exist to connect proton donors and acceptors. The accessibility of proton transfer pathways to the N- and P-sides of the membrane must also change during the reaction cycle to ensure that the proton transfers do not dissipate the proton gradient. The gates that change the conductivity of proton transfer have been difficult to identify as they must be transient and may occur anywhere along the proton transfer pathways. MCCE (Multiconformation Continuum Electrostatics) has been used to access the proton affinity of key groups through the reaction cycle in cytochrome c oxidase and bacteriorhodopsin. Motifs that help groups gain and loose protons will be described. In addition, proton transfer pathways are identified through Monte Carlo sampling and the energy of intermediates are described. Funded by DOE DE-SC0001423 and NSF MCB-1519640.
Host: Angel E. Garcia