One amino acid's quick flip maintains a one-way flow of protons across the mitochondrial membrane, according to Ville Kaila, Marten Wikström (University of Helsinki, Finland), and colleagues.
ATP production in mitochondria depends on maintaining a proton gradient across the inner membrane. To establish this gradient, protons are drawn up from the mitochondrial matrix through the interior of cytochrome c oxidase, to a glutamic acid residue in the core of the protein (position 242). This glutamic acid was known to act as a switch—in its down position it accepts protons, while in its up position it sends most protons up the concentration gradient to accumulate in the intermembrane space (it also diverts some protons to the enzyme's heme group, where they react with oxygen, making water and powering the whole process). But a key question has been how the enzyme keeps protons from flowing backward, down their concentration gradient.
Using molecular dynamics simulations, the team now shows that the preferred orientation of the glutamic acid switch depends heavily on its protonation state. With a proton attached, it was equally stable pointing either up or down. But once the proton detached, the side chain flipped back down in a picosecond. “The unprotonated glutamic acid prefers the down state by a factor of at least ten thousand,” Wikström says. Its rapid movement takes it quickly out of reach of the proton it has just dropped off, and thus it serves as a one-way valve for proton transfer.