The active transport of ions across a membrane by an ATP-driven electrogenic ion pump is often described by an 'alternate access' model. The position of the binding site is assumed to be unchanged as the binding cavity opens alternatively to the uptake and discharge sides of the membrane. The ion binding affinity is higher on the uptake side of the membrane than on the discharge side. This difference in affinities is related to the maximum transport rate and to the efficiency with which ATP hydrolysis is coupled to active transport. Here we examine the electrostatic contribution to binding affinities, using a simple geometry for a model membrane-protein system, a continuum dielectric approximation, and a numerical method to calculate binding energy as a function of the binding site location. If the binding site is located asymmetrically, being further from the uptake side of the membrane than from the discharge side, there is a significant difference in binding free energy between the uptake and discharge states. This asymmetry can produce differences in affinities that are consistent with those measured for biological active transport systems. These results may account for the observed asymmetric location of the calcium binding site in the calcium ATPases from sarcoplasmic reticulum and from the plasma membrane. Electrostatic energy differences associated with binding site asymmetry may be a general feature of electrogenic transmembrane ion pumps. © 1995.
Hao, M. H., & Harvey, S. C. (1995). Active transport of ions across membranes: energetic role of electrostatics and binding site asymmetry. BBA - Biomembranes, 1234(1), 5–14. https://doi.org/10.1016/0005-2736(94)00265-Q