Mechanism of the light-driven proton pump of bacteriorhodopsin based on the consistency principle.

Abstract

According to the consistency principle, a design principle for protein tertiary structures, all interactions that maintain a protein’s structure are consistent with each other. We assume that proteins satisfy the consistency principle. The specific local structures that form are consequences of the consistency principle. The specific local structures and the global conformation become interdependent. We assume that protein function is a consequence of the interdependency and the breaking of consistency. We applied this idea to the light-driven proton-pump mechanism of bacteriorhodopsin. Bacteriorhodopsin has two distinct conformers: one in which the proton channel opens toward the extracellular side, and another in which the channel opens toward the cytoplasmic side. Important reactions involved in proton pumping are protonation of D85 from the retinal Schiff base and reprotonation of the Schiff base from D96. To recruit a key water molecule, a characteristic pentameric hydrogen bond network is formed around the D85 and Schiff base, but is lost during proton pumping. These reaction components can be explained by active consistency-breaking and processes that either establish new consistency or restore the original consistency. Thus, the consistency principle can be expanded from structure to guide our understanding of protein function. This hypothesis is applicable to other functional proteins with two distinct conformers.