Poul Nissen
Resources:
The Kavli Symposia
"The Structure and Function of Ion Pumps in Cells and Changes in Disease"
P-type ATPase cation pumps energise the biomembranes by establishing and maintaining steep electrochemical gradients and are essential to all eukaryotes. Na+,K+-ATPase is a prominent member and its activitiy accounts for nearly 2/3 of the ATP turnover in the brain maintaining the Na+ and K+ gradients and energizing the formation of membrane potentials.
The first crystal structure of the Na+,K+-ATPase was determined in the potassium-bound form at 3.5 Å resolution. It consists of the alpha-subunit providing the ATPase coupled ion transport, a heavily glycosylated beta subunit, and a small regulatory gamma subunit (FXYD protein). Na+,K+-ATPase is electrogenic as it pumps three sodium ions out and two potassium ions into the cell per ATP hydrolysed, but how does it do that? From the structure we discovered that the C-terminus of the alpha-subunit may provide a key element of function which affects in particular Na+ transport. Indeed, our electrophysiological studies show a profound effect of the C-terminus and an associated ion pathway leading to an ion binding site which controls the electrogenic transport properties and Na+ site 3. The importance of these findings are underscored by the fact that a large cluster of neurological disease mutations of Na+,K+-ATPase map to this region of the pump. Based on these data we present a revised model of the transport mechanism of Na+,K+-ATPase.
