In silico studies provide new structural insights into trans-dimerization of β1 and β2 subunits of the Na+, K+-ATPase.

The Na+, K+-ATPase is an electrogenic transmembrane pump located in the plasma membrane of all animal cells. It is a dimeric protein composed of α and β subunits and has a third regulatory subunit (γ) belonging to the FXYD family. This pump plays a key role in maintaining low concentration of sodium and high concentration of potassium intracellularly. The α subunit is the catalytic one while the β subunit is important for the occlusion of the K+ ions and plays an essential role in trafficking of the functional αβ complex of Na+, K+-ATPase to the plasma membrane. Interestingly, the β1 and β2 (AMOG) isoforms of the β subunit, function as cell adhesion molecules in epithelial cells and astrocytes, respectively. Early experiments suggested a heterotypic adhesion for the β2. Recently, we reported a homotypic trans-interaction between β2-subunits expressed in CHO cells. In this work we use In Silico methods to analyze the physicochemical properties of the putative homophilic trans-dimer of β2 subunits and provide insights about the trans-dimerization interface stability. Our structural analysis predicts a molecular recognition mechanism of a trans-dimeric β2 - β2 subunit and permits designing experiments that will shed light upon possible homophilic interactions of β2 subunits in the nervous system.