Ion transport and energy transduction of P-type ATPases studied by simulations

Abstract

P-type ATPases actively transport cations across the membrane. The basic mechanisms of ion transport and energy transduction are supposed to be the same in all P-type ATPases. Both reaction mechanisms were studied computationally for the Ca2+-ATPase and Na+/K+-ATPase. The Ca2+ transport of the Ca2+-ATPase is associated with a proton countertransport from the SR to the cytoplasm. Binding of the protons is thought to take place at acidic residues in the binding sites. The protonation of acidic ligands were analyzed in different enzyme states of the Ca2+-ATPase by multiconformation continuum electrostatic calculations. Glu771, Asp800 and Glu908 are prime candidates for the proton countertransporting residues and are likely to receive and release their proton via the same path. The Glu309 instead might serve as a proton shuttle between Ca2+ binding site I and the cytoplasm. The reaction cycle of P-Type ATPases is physiologically initiated by the binding and hydrolysis of ATP but can also be induced experimentally by voltage jumps across the membrane. We simulated the applied electric field by an “ionic capacitor” and studied the impact on different enzyme states of the Ca2+-ATPase and the Na+/K+-ATPase by a combination of MCCE and MD. A selective activation of specific helices in response to the electric field is observed.