Structure and function of the Na,K pump: ten years of molecular biology

The cloning of the cDNAs encoding the subunits of the Na,K pump over 10 years ago has enabled us to apply the techniques of molecular biology to questions of structure and function within this complex transport protein. The cloning efforts provided the primary structures of the alpha and beta subunits, from which the probable topology of the proteins within the membrane were deduced. Site-directed mutagenesis of the cDNAs, together with subsequent expression of the mutant DNA in heterologous systems, has identified many of the residues involved in ligand binding and catalytic turnover. Isolation and characterization of multiple cDNAs encoding the pump subunits has confirmed the presence of subunit isoforms suggested by earlier biochemical data. Additional experiments with mutagenesis and expression systems have identified regions of the alpha and beta subunits required for assembly of the pump complex.