Crucial new insight into sodium-potassium pumps
The sodium-potassium pump is a vital enzyme found in all human cells that maintains an exact balance of sodium and potassium ions on either side of the cell membrane. The pump is required for several vital processes, such as the transport of nutrients into the cell, and any malfunction is closely linked to disease. A malfunctioning pump in brain cells results in severe neurological conditions such as migraine with aura, muscle spasms or one-sided paralysis (hemiplegia).
In a recently published study in Science, researchers from Aarhus University, KTH Royal Institute of Technology and Stockholm University at SciLifeLab presented structural information on the sodium-potassium pump in its sodium-binding state that is essential for our understanding of illness and for the development of new medicines.
Sodium ions are difficult to detect unambiguously with a single method and an interdisciplinary approach was therefore applied to describe ion binding within the pump by several techniques. Researchers at Aarhus University solved the structure of the pump using X-ray crystallography and proposed three ion-binding sites containing sodium ions. Similar sites were also observed using electrophysiology measurements. Researchers at KTH/SciLifeLab used theoretical simulation models to provide a dynamic view of the pump at an atomic level and confirmed the existence of the three ion-binding sites.
“Because an X-ray structure provides a static view of the enzyme structure, it is also crucial to account for structural dynamics in the system. The supercomputer Lindgren at KTH, which is ranked in 31st place among the 500 most powerful computer systems in the world, enables us to go beyond a static structure and characterize structural rearrangements in highly complex biological systems like the sodium-potassium pump”, says Magnus Andersson, researcher in the Biophysics group lead by Professor Erik Lindahl at SciLifeLab.
Together, these studies reveal details of sodium binding that will be crucial to better understand structure-function relations of ion-exchange, transport and how the mechanism is affected by disease-related mutations.
Publication:
Crystal Structure of Na+, K+-ATPase in the Na+-Bound State
M Nyblom, H Poulsen, P Gourdon, L Reinhard, M Andersson, E Lindahl, N Fedosova, P Nissen
Science 4 October 2013: Vol. 342 no. 6154 pp. 123-127, DOI: 10.1126/science.1243352
