SPring-8, the large synchrotron radiation facility

The steric structure of the sodium-potassium pump, the target molecule of digitalis, a medicine used for cardiac failure, and essential for neural excitation, was clarified for the first time in the world using the SPring-8 beamline BL41XU (Structural Biology I Beamline).

In all animal cells, differences in the concentrations of sodium (Na⁺), potassium (K⁺), calcium (Ca²⁺), and other ions inside and outside the cells are maintained within a certain range, which is a key factor for vital activities. For example, the phenomenon of neural excitation is caused by the following mechanism: the extracellular concentration of Na⁺ is normally higher than its intracellular concentration; when Na⁺ flows inside the cells in accordance with its concentration gradient, an action potential causing an electrical signal is induced. The concentration gradient which is eliminated following neural excitation, is again returned to its original level by ion-pump proteins. In this study, the scientists elucidated the steric structure of the sodium-potassium pump, a protein that transports Na⁺ from inside to outside the cell and K⁺ from outside to inside the cell by utilizing the energy from ATP. Proteins in the same group include the Ca²⁺ pump, the structure of which was determined by the research group led by Professor Toyoshima. The sodium-potassium pump is such an important protein that J. C. Skou (Denmark) was awarded the 1997 Nobel Prize in Chemistry for his discovery of the pump. This pump is the target protein protein of the digitalis group, the active ingredient in a medicine that has been prescribed as a cardiotonic agent for more than 200 years. This pump has also attracted attention as a target protein of new medicines because it has been clarified to be closely related to high-blood pressure and cancer as well as cardiac failure. The development of new medicines is expected to advance markedly following the clarification of the protein pump's atomic structure in this study.

This study was supported by a Grant-in-Aid for Specially Promoted Research (Structural Biology of Ion Transporters) and SPring-8 Long-Term Proposals (Crystallographic Clarification of Membrane Transporter Action Mechanism).

The results of this research were published in the British scientific journal Nature on 21 May 2009.

Publication:
"Crystal structure of the sodium-potassium pump at 2.4 Å resolution"
Takehiro Shinoda, Haruo Ogawa, Flemming Cornelius & Chikashi Toyoshima
Nature 459, 446-450 (2009), published 21 May 2009.