Coupling mechanisms in ATP-driven pumps.

Abstract

Because the kinetic reaction schemes for primary and secondary active transport can be identical, the same fundamental relationship holds among rate and equilibrium constants: the ratio of coupled to uncoupled flux is no greater than the ratio of substrate dissociation constants in an initial complex and a conformationally altered state. Further, the role played by each substrate in coupling depends in the same way on its order of addition to the carrier. It follows that the structural principles governing the design and operation of the carrier proteins are fundamentally alike. In either system, the strict control of the mobility and specificity of the carrier, a prerequisite for active transport, depends on the utilization of substrate binding forces to alter the protein conformation; and whether the driving substrate is transported or not and whether reversibly bound or covalently bound (like the phosphate group derived from ATP), the force producing the conformational change is derived from non-covalent interactions between the substrate (held at the substrate site) and other sections of the protein. The protein probably encloses the substrate, with a resulting increase in the binding force; the favourable energy of interaction balances the unfavourable energy involved in distorting the protein structure. The postulated complex can account for the 'occluded state' of transported cations and for the favourable reaction of inorganic phosphate with the calcium pump.