Significance of the beta-subunit in the biogenesis of Na+/K(+)-ATPase.
This review summarizes our experiments on the significance of the beta-subunit in the functional expression of Na+/K(+)-ATPase. The beta-subunit acts like a receptor for the alpha-subunit in the biogenesis of Na+/K(+)-ATPase and facilitates the correct folding of the alpha-subunit in the membrane. The alpha-subunit synthesized in the absence of the beta-subunit is subjected to rapid degradation in the endoplasmic reticulum. Several assembly sites are assigned in the sequence of the beta-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 beta-subunit confers a resistance to trypsin on the alpha-subunit. The conformations induced in the alpha-subunit of Na+/K(+)-ATPase by Na+/K(+)- and H+/K(+)-ATPase beta-subunits are somehow different from each other and are named the NK-type and KH-type, respectively. The extracellular domain of the beta-subunit is involved in the folding of the alpha-subunit leading to trypsin-resistant conformations. The sequences from Cys150 to the COOH-terminus of the Na+/K(+)-ATPase beta-subunit and from Ile89 to the COOH-terminus of the H+/K(+)-ATPase beta-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 beta-subunits is critical in the expression of functional Na+/K(+)-ATPase.
Ueno
S
S
Department of Biology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Takeda
K
K
Noguchi
S
S
Kawamura
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*
D000254:Sodium-Potassium-Exchanging ATPase