Crystal structure of the sodium–potassium pump

Abstract

The Na+,K+-ATPase generates electrochemical gradients for sodium and potassium that are vital to animal cells, exchanging three sodium ions for two potassium ions across the plasma membrane during each cycle of ATP hydrolysis. Here we present the X-ray crystal structure at 3.5 A resolution of the pig renal Na+,K+-ATPase with two rubidium ions bound (as potassium congeners) in an occluded state in the transmembrane part of the alpha-subunit. Several of the residues forming the cavity for rubidium/potassium occlusion in the Na+,K+-ATPase are homologous to those binding calcium in the Ca2+-ATPase of sarco(endo)plasmic reticulum. The beta- and gamma-subunits specific to the Na+,K+-ATPase are associated with transmembrane helices alphaM7/alphaM10 and alphaM9, respectively. The gamma-subunit corresponds to a fragment of the V-type ATPase c subunit. The carboxy terminus of the alpha-subunit is contained within a pocket between transmembrane helices and seems to be a novel regulatory element controlling sodium affinity, possibly influenced by the membrane potential.

Steroid-like compounds in Chinese medicines promote blood circulation via inhibition of Na+/K+-ATPase

“…To reveal the observed difference in Na + ,K + -ATPase inhibition at molecular level, the examined steroid-like compounds were subjected to molecular modeling and docking, as exemplified by bufalin and ursolic acid, to the extracellular domain of Na + ,K + -ATPase α subunit. As expected from structural similarity, the interaction of bufalin with the binding pocket of Na + ,K + -ATPase nearly matched to that of ouabain reported previously [7] with the unique lactone ring (indicated by a pink arrow) penetrating deeply into the cavity close to two K + binding sites ( Figure 4A). Comparably, the hydrophobic steroidal core of ursolic acid was confined in a location similar to that of bufalin within the binding pocket of Na + ,K + -ATPase ( Figure 4B).…”

“…The crystal structures of pig renal Na + ,K + -ATPase (PDB code 3B8E) and shark rectal gland Na + ,K + -ATPase (PDB code 3A3Y) were downloaded from Protein Data Bank and found to posses equivalent structures [7,8] . In order to facilitate docking process, the β and γ subunits of the Na + ,K + -ATPase were removed, as well as the water molecules and counter-ions surrounding the remaining α subunit.…”

Interaction between human cytomegalovirus UL136 protein and ATP1B1 protein

“…Na, K-ATPase consists of α and β subunits. The glycosylated β subunit has been proposed to facilitate the assembly and transport of the α subunit from the endoplasmic reticulum to the plasma membrane (20,21), and the β subunit is the key factor in polarizing distribution of Na, K-ATPase (22). The results of the present study showed that the HCMV UL136 protein has the ability to interact with ATP1B1.…”

Stabilisation of Na,K-ATPase structure by the cardiotonic steroid ouabain

“…Crystal structures of pig and shark Na,K-ATPase in both the absence [3,4] and presence of ouabain [5,6] have been determined. There is a strong similarity between the structures of the shark and pig a-subunits, and ouabain-induced re-arrangements can be seen for the enzymes from both species.…”