Protein structure revealed that gives clues to fight malaria
01 October 2012
For the first time, researchers have been able to determine the three-dimensional structure of an important membrane protein that regulates the ion balance of cells. The findings open up new possibilities to fight diseases such as malaria and sleeping sickness and have recently been published in the journal Science.Using the synchrotron radiation technology at the MAX IV Laboratory in Lund, Sweden, Professor Adrian Goldman’s research team at the University of Helsinki has been able to determine the structure of the protein.
The protein, which is called a pyrophosphatase, is a membrane protein found in plants and bacteria and in protozoan parasites. The protein has an important role in maintaining the right balance of ions in cells. In parasites, a proper ion balance is essential for them to be able to invade and live in other organisms.
Pyrophosphatases are also important in development and maturation processes. For instance, they help plants survive under stress conditions such as drought, cold weather or low light conditions.
Pyrophosphatases are absent in mammals and humans, which makes them attractive targets for the pharmaceutical industry. Knowledge of the structure of the protein provides important clues to design future drugs to treat diseases such as malaria and sleeping sickness.
“Knowledge of the structure of pyrophosphatases increases our general knowledge of membrane proteins. Despite the fact that over 50 per cent of the pharmaceutical drugs on the market interact with membrane proteins, we have very limited knowledge of how they function compared with soluble proteins. For example, over 80 000 three-dimensional protein structures are known, but only 357 of these are membrane proteins”, says Marjolein Thunnissen, head of research at experiment station I911-3 on the MAX II ring at the MAX IV Laboratory in Lund.
Now that the researchers have determined the structure of the pyrophosphatases, they have discovered that these proteins use a different mechanism for pumping ions through a membrane than has been found in other classes of membrane protein.
For a protein to pump ions through a cell membrane it requires energy, and the pyrophosphatases use a phosphate-rich molecule (pyrophosphate) as their energy source. The molecule is split in the process, and this releases energy which enables the protein to move and pump the ions through the membrane.
The process the protein uses is ingenious, since pyrophosphates are a natural waste product; by using a waste product as a source of energy, the cell becomes more efficient.
The researchers from Professor Adrian Goldman’s research team at the University of Helsinki gathered data for the ‘sodium-pumping pyrophosphatase’ protein at station I911-3 on the MAX II ring at the MAX IV Laboratory in Lund and at multiple stations of the ESRF in Grenoble, France.
Read more about the MAX IV Laboratory
About the MAX IV Laboratory
The MAX IV Laboratory in Lund, Sweden, is a national research laboratory comprising of MAX-lab and the MAX IV-project. The MAX IV project opens new possibilities for cutting-edge research within broad areas of science, for example materials science, structure biology and nano technology.
MAX IV will be the next generation synchrotron light facility and will replace the existing laboratory, i.e. the storage rings MAX I, II and III. The MAX IV Laboratory has developed out of the accelerator research that has been executed at the Lund University since the 1960’s; Lund University in Sweden is the host University for the Facility.