Structure-function studies of the sodium pump

The Na+,K+-ATPase is an ubiquitous plasma membrane protein complex that bel ongs to the P-type family of ion motive ATPases. Under normal conditons, it couples the hydrolysis of one molecule of ATP to the exchange of three Na for two K+ ions, thus maintaining the normal gradient of these cations in animal cells. Despite decades of investigation of its structure and functio n, the structural basis for its cation specificity and for conformational c oupling of the scalar energy of ATP hydrolysis to the vectorial movement of Na+ and K+ have remained a major unresolved issue. This paper summarizes o ur recent studies concerned with these issues. The findings indicate that r egions(s) of the amino terminus and first cytoplasmic (M2/M3) loop act syne rgisticaly to affect the steady-state conformational equilibrium of the enz yme. Although carboxyl- or hydroxyl-bearing amino acids comprise the cation -binding and occlusion sites, our experiments also suggest that these inter actions may be modulated by juxtapositioned cytoplasmic regions.