Allosteric property of the (Na++K+)-ATPase β1 subunit

(Na++K+)-ATPase (NKA) comprises two basic α and β subunits: The larger α subunit catalyzes the hydrolysis of ATP for active transport of Na+ and K+ ions across the plasma membrane; the smaller β subunit does not take part in the catalytic process of the enzyme. Little is known about allosteric regulation of the NKA β subunit. Here, we report a surprising finding that extracellular stimuli on the native β1 subunit can generate a significant impact on the catalytic function of NKA. By using a β1 subunit-specific monoclonal antibody JY2948, we found that the JY2948–β1 subunit interaction markedly enhances the catalytic activity of the enzyme and increases the apparent affinity of Na+ and K+ ions for both ouabain-resistant rat NKA and ouabain-sensitive dog NKA. This study provides the first evidence to identify an allosteric binding site residing on the NKA β1 subunit and uncovers the latent allosteric property of the β1 subunit, which remotely controls the NKA catalytic function.

► (Na++K+)-ATPase β1 subunit contains allosteric site and possesses allosteric property. ► Activator JY2948 is capable of inducing the JY2948–β1–α1 interaction complex. ► Binding of JY2948 to β1 alters apparent Na+/K+ affinity and enhances enzyme activity. ► β1 remotely controls enzyme function through the protein–protein interaction.