Significance of the β-Subunit in the Biogenesis of Na⁺/K⁺-ATPase

Abstract

This review summarizes our experiments on the significance of the β-subunit in the functional expression of Na⁺/K⁺-ATPase. The β-subunit acts like a receptor for the α-subunit in the biogenesis of Na⁺/K⁺-ATPase and facilitates the correct folding of the α-subunit in the membrane. The α-subunit synthesized in the absence of the β-subunit is subjected to rapid degradation in the endoplasmic reticulum. Several assembly sites are assigned in the sequence of the β-subunit from the cytoplasmic NH₂-terminal domain to the extracellular COOH-terminus: the NH₂-terminal region of the extracellular domain, the conservative proline in the third disulfide loop, the hydrophobic amino acid residues near the COOH-terminus and the cysteine residues forming the second and the third disulfide bridges. Upon assembly, the β-subunit confers a resistance to trypsin on the α-subunit. The conformations induced in the α-subunit of Na⁺/K⁺-ATPase by Na⁺/K⁺- and H⁺/K⁺-ATPase β-subunits are somehow different from each other and are named the NK-type and KH-type, respectively. The extracellular domain of the β-subunit is involved in the folding of the α-subunit leading to trypsin-resistant conformations. The sequences from Cys150 to the COOH-terminus of the Na⁺/K⁺-ATPase β-subunit and from Ile89 to the COOH–terminus of the H⁺/K⁺-ATPase β-subunit are necessary to form trypsin-resistant conformations of the NK- and HK-type. respectively. The first disulfide loop of the extracellular domain of the β-subunits is critical in the expression of functional Na⁺/K⁺-ATPase.