Abstract
The Na+, K+-ATPase transports Na+ and K+ across the membrane of all animal cells. In addition to its ion transporting function, the Na+, K+-ATPase acts as a homotypic epithelial cell adhesion molecule via its β1 subunit. The extracellular region of the Na+, K+-ATPase β1 subunit includes a single globular immunoglobulin-like domain. We performed Molecular Dynamics simulations of the ectodomain of the β1 subunit and a refined protein-protein docking prediction. Our results show that the β1 subunit Ig-like domain maintains an independent structure and dimerizes in an antiparallel fashion. Analysis of the putative interface identified segment Lys221-Tyr229. We generated triple mutations on YFP-β1 subunit fusion proteins to assess the contribution of these residues. CHO fibroblasts transfected with mutant β1 subunits showed a significantly decreased cell-cell adhesion. Association of β1 subunits in vitro was also reduced, as determined by pull-down assays. Altogether, we conclude that two Na+, K+-ATPase molecules recognize each other by a large interface spanning residues 221–229 and 198–207 on their β1 subunits.
Highlights
The Na+, K+-ATPase or sodium pump (Na+-K+) is a multimeric protein responsible for the electrochemical gradient of all animal cells
We propose that the Na+, K+-ATPase associates in trans mainly through residues 198–207 and 221–229 in its β1 subunit
We have studied the adhesive function of NaK β1 subunit in the epithelial MDCK cell line derived from dog kidney [7,8,10,13]
Summary
The Na+, K+-ATPase or sodium pump (Na+-K+) is a multimeric protein responsible for the electrochemical gradient of all animal cells. It is composed of α, β and γ subunits. The α-subunits transport the cations and couple them to the hydrolysis of ATP and it is considered to be the catalytic subunit of the enzyme [1,2]. Four isoforms of the catalytic subunit are known, α1–α4 [3]. The β subunit is a glycosylated type II membrane protein It is necessary for the proper folding, traffic, and insertion of the Na+, K+-ATPase into the plasma membrane. Three isoforms of β (β1–β3) of NaK are known [4]
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