Structural Requirements for Subunit Assembly of the Na, K-ATPase

This chapter discusses the ideas and experiments on the problem of subunit assembly of the Na,K-adenosine triphosphate (ATP)ase and its relation to upregulation. The minimal functional unit of the Na,K-ATPase appears to be an α–β complex. Some aspects of assembly, particularly the possible role of the β-subunit, in the proper folding of the α-subunit and intermediate conformations during the assembly process, are well researched. The studies on the structural requirements in the β-subunit for subunit assembly illustrate the fact that most information can be gained from the subunit forms that do assemble. In cases where assembly is prevented, there remains uncertainty whether to ascribe the deficit to loss of a critical region for assembly or to secondary phenomena, such as improper folding of the subunit, interaction with binding protein (BIP), or metabolic destabilization. An approach that attempts to avoid these secondary problems is the construction of chimeric proteins for the catalytic subunit, using parts from catalytic subunits of different E1E2 ATPases. The chimera approach has also been used to examine subunit assembly, but the chimeras involve the Na,K-ATPase α-subunit and the SR/ER-type Ca-ATPases. The Ca-ATPases lack a β-type subunit. They are expressed in cells that also express the Na,K-ATPase and no aberrant association of the Na,K-ATPase β-subunit, with the Ca-ATPase, has ever been seen.