Mechanism of the sodium-potassium pump revealed

Oct 04, 2013
The figure shows the tunnel-like entry point to the binding sites of the sodium-potassium pump in the sodium-bound state. The three small sodium ions are bound inside the pump (violet spheres to the left), whereas there is not sufficient room for the larger potassium ions (green spheres to the right). The blue web shows the inner surface of the protein blocking the potassium ions. The letter code indicates the amino acids shown in the pump, which are essential to the binding process. Credit: Bente Vilsen and Flemming Cornelius

Researchers from Aarhus University have collaborated with a Japanese group of researchers to establish the structure of a crucial enzyme—the so-called sodium-potassium pump—which forms part of every cell in the human body. The result, which was recently published in Nature, may pave the way for a better understanding of neurological diseases.

It's not visible to the naked eye and you can't feel it, but up to 40 per cent of your body's energy goes into supplying the microscopic sodium-potassium pump with the energy it needs. The pump is constantly doing its job in every cell of all animals and humans. It works much like a small battery which, among other things, maintains the sodium balance which is crucial to keep muscles and nerves working.

The sodium-potassium pump transports sodium out and potassium into the cell in a fixed cycle. During this process the of the pump changes. It is well-established that the pump has a sodium and a potassium form. But the structural differences between the two forms have remained a mystery, and researchers have been unable to explain how the pump distinguishes sodium from potassium.

Structure solves the mystery

Thanks to the international collaboration between Professor Chikashi Toyoshima's group at the University of Tokyo and researchers from Aarhus University, the structure of the sodium-bound form of the protein has now been described. For the first time ever, the sodium ions can be studied at a resolution so high - 0.28 nanometres - that researchers can actually see the sodium ions and observe where they bind in the structure of the pump. In 2000, Professor Chikashi Toyoshima's group described the structure of a calcium-pump for the first time, and in 2007 and 2009 research groups from Aarhus University and Toyoshima's group described the potassium-bound form of the sodium-potassium pump.

"The new protein structure shows how the smaller are bound and subsequently transported out of the cell, whereas the access of the slightly larger potassium ions is blocked. We now understand how the pump distinguishes between sodium and potassium at the molecular level. This is a great leap forward for research into ion pumps and may help us understand and treat serious neurological conditions associated with mutations of the , including a form of Parkinsonism and alternating hemiplegia of childhood in which sodium binding is defective," explains Bente Vilsen, a professor at Aarhus University who spearheaded the project's activities in Aarhus with Associate Professor Flemming Cornelius.

Impressed Nobel Prize winner

The vital pump was discovered in 1957 by Professor Jens Christian Skou of Aarhus University, who received the Nobel Prize for his discovery in 1997. The new result is the culmination of five or six decades of research aimed at the mechanism behind this vital motor of the cells.

"Years ago, when the first electron microscopic images were taken in which the enzyme was but a millimetre-sized dot at 250,000 magnifications, I thought, how on earth will we ever be able to establish the structure of the enzyme. The pump transports potassium into and sodium out of the cells, so it must be capable of distinguishing between the two ions. But until now, it has been a mystery how this was possible," says retired Professor Jens Christian Skou, who - even at 94 years of age - keeps up to date with new developments in the field of research which he initiated more than 50 years ago.

"Now, the researchers have described the structure that allows the enzyme to identify sodium and this may pave the way for a more detailed understanding of how the pump works. It is an impressive achievement and something I haven't even dared dream of," concludes Jens Christian Skou.

Explore further: Crucial new insight into the secrets of Nobel Prize-winning pump

More information: www.nature.com/nature/journal/vaop/ncurrent/full/nature12578.html

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User comments : 5

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HannesAlfven
1.4 / 5 (10) Oct 04, 2013
Note that polymers have been observed to exhibit the same exact gating attributes, calling into question the premise itself ... See the work of Gerald Pollack at the University of Washington.
barakn
3 / 5 (4) Oct 04, 2013
Since the protein that makes up the sodium-potassium pump is a polymer, and the lipids making up the lipid bilayer in which the pump is embedded are polymers, your comment about polymers is moot.
HannesAlfven
1 / 5 (8) Oct 04, 2013
Re: "Since the protein that makes up the sodium-potassium pump is a polymer, and the lipids making up the lipid bilayer in which the pump is embedded are polymers, your comment about polymers is moot."

Okay, but Pollack points out that gels come with a natural ability to maintain voltage gradients. No pumps or channels are required to make it happen. Can you help me to understand then why it is that 40% of the body's energy must be spent maintaining these charge differentials with these pumps and channels if this functionality is already apparently a feature of gels?

I'm actually admittedly confused, and would love to be corrected. Gerald's publications are really quite simple to understand compared to this ...
zeplinair
5 / 5 (2) Oct 04, 2013
HannesAlfven:The previous phenomena you mention do not require energy. Maintaining the Na+/K+ gradient however does as it is necessary to change this gradient suddenly, and then re-establish it for the function of many cells, especially neurons. Gates are opened to suddenly change the gradient it to produce the electrical action potential. The pump is then used to re-establish the gradient to the membranes resting potential that allows another action potential to happen. This active pumping against the gradient (so opening channels will suddenly change it) requires the energy of ATP.
barakn
not rated yet Oct 05, 2013
A gel would have a static electric field, and if immersed in a solution containing mobile ions both positive and negative, the ions would migrate until the electric field was neutralized. Gerald and Hannes seem to be unaware that these gradients need a purpose or an organism wouldn't produce them. They are used to move things around, and the natural result of this is for the the gradients to be sapped and exhausted unless something actively regenerates them. For the neutralized gel I first mentioned, the gel would have to be pulled apart and built from scratch to regenerate the voltage gradient. Talk about energetically intensive - why complain about the energy use of pumps and channels when your own stupid theory is energetically worse?

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