Homology modeling of Na,K-ATPase: a putative third sodium binding site suggests a relay mechanism compatible with the electrogenic profile of Na+ translocation.
Identification of the third Na(+) binding site would be crucial in interpretation of the electrophysiological behavior of Na,K-ATPase. To address this question a three-dimensional homology model of Na,K-ATPase was built from the known crystallographic structure of Ca-ATPase (1EUL). Phe760, which is conserved in virtually all Ca-ATPases, is replaced by Ser768 in Na,K-ATPase, resulting in a small cavity between M4, M5, and M6. A partially hydrated Na(+) ion can be bound at this third site on the cytoplasmic side of cation binding sites 1 and 2. This leads to the proposal that the conductance of the "third Na(+)" ion across approximately 70% of the membrane dielectric may be achieved by adding up the passage of one Na(+) ion from the described cytoplasmic cavity to cation site 1 and the further conductance of the previously bound Na(+) ion from cation site 1 to the extracellular phase. This relay mechanism may therefore be compatible with the electrogenic profile of Na(+) translocation.
Håkansson
K O
KO
Biomembrane Center, August Krogh Institute, University of Copenhagen, Denmark. kohakansson@aki.ku.dk
Jorgensen
P L
PL
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001693:Biological Transport, Active; D000252:Calcium-Transporting ATPases / Q000737:chemistry; D017124:Conserved Sequence; D007700:Kinetics; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry* / Q000378:metabolism*
D012964:Sodium; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase