ATP-induced conformational changes of the nucleotide
binding domain of Na,K-ATPase
The Na,K-ATPase hydrolyses ATP in order to drive the
coupled extrusion and uptake of Na+ and K+ ions across the
plasma membrane. Here, we report two high-resolution NMR
structures of the 213-residue nucleotide binding domain of
rat a1 Na,K-ATPase, determined in the absence and the
presence of ATP. The nucleotide binds in the
anti-conformation and shows a relative paucity of
interactions with the protein which reflects the
low-affinity ATP-binding state. Binding of ATP induces
substantial conformational changes in the binding pocket
and for residues located in the hinge region connecting the
N- and P-domain. Comparison with the Ca-ATPase in the
E2(TG) and the model of H-ATPase in the E1 form reveals a
resemblance of the conformation of the hinge with the
native and ATP-bound form of the N-domain of Na,K-ATPase,
respectively. Thus, ATP-binding induces a conformational
change that likely triggers a series of events necessary
for the release of the K+ ions and/or disengagement of the
A-domain leading to the eventual transfer of the
g-phosphate group to the invariant Asp 369.
PDB codes 1MO7 (native) (
Download) and 1MO8 (complex). (
Download)
■ Hilge, M, Siegal, G., Vuister, G.W., Guntert, P.,
Gloor, S.M. & Abrahams, J.P. (2003) “ATP-induced
conformational changes of the nucleotide binding domain of
Na,K-ATPase”,
Nature Struct. Biol.
10, 468-474.
