The C Terminus of Na+,K+-ATPase Controls Na+ Affinity on Both Sides of the Membrane through Arg935

Abstract

from the external side of the membrane but is involved in stabilization of the E 2 form. These data demonstrate that the C terminus controls Na ؉ affinity on both sides of the membrane and suggest that Arg 935 constitutes an important link between the C terminus and the third Na ؉ site, involving an arginine-stacking interaction between Arg 935 and the C-terminal tyrosines. Lys 768 may interact preferentially with the C terminus in E 1 and E 1 P forms and with the loop between transmembrane segments M6 and M7 in E 2 and E 2 P forms.

Critical roles of isoleucine-364 and adjacent residues in a hydrophobic gate control of phospholipid transport by the mammalian P4-ATPase ATP8A2

“…This complex substrate dependence, characterized by activation at low substrate concentration and inhibition at high substrate concentration, is reminiscent of the K + dependence of the Na + ,K + -ATPase, where K + activates the enzyme by binding at the externally facing sites of E 2 P and inhibits at higher concentration by binding at the internally facing sites of E 1 in competition with Na + , driving the enzyme into the K + -occluded E 2 state (10,32,33). On stabilizing the E 2 state by mutation, the K + inhibition of the Na + ,K + -ATPase activity becomes very pronounced, occurring at rather low K + concentration (34).…”

Altered Na + transport after an intracellular α-subunit deletion reveals strict external sequential release of Na + from the Na/K pump

“…During revision of this article, a paper describing the effects of ⌬KETYY in nonsided membrane preparations was published online (35).…”

Rescue of Na+ Affinity in Aspartate 928 Mutants of Na+,K+-ATPase by Secondary Mutation of Glutamate 314

“…1). Site III interacts functionally with the C terminus of the protein (4,6). The three Na ϩ ions bind cooperatively, and the crystal structure predicts that the first Na ϩ binds at site III with site I and II being filled consecutively thereafter, the occupation of site II leading to activation of phosphoryl transfer from bound ATP (3).…”