Progress made in structure determination

In recent years, several research teams from Stockholm University have made progress in their efforts to determine the structure of human membrane proteins using different methods. One of the greatest challenges is to combine better methods for protein expression, purification, and crystallisation using modern computer-based methods, such as bioinformatics and simulations.

The biggest challenge when it comes to determining crystal structures is that it is far from certain that the researchers will manage to obtain crystals, and even if they do, there is a risk that some of the membrane proteins will be too unstable for the crystals to be arranged properly.

Possible to detect with higher resolution

To avoid these problems, the researchers can also use cryo-EM, where they rapidly freeze a small membrane sample and use an electron microscope to take pictures of individual proteins. Traditionally, this method has only resulted in low-resolution structures, but a new cryo-EM facility at Stockholm University will enable researchers to use a new generation of tools to detect electrons directly with much higher resolution. By combining thousands of images with computer models, the researchers will be able to gradually obtain information on what the structures look like, what states they appear in, and how membrane proteins interact with each other.

David Drew

David Drew

“This is a fantastic way to combine the progress made in modern bioinformatics and simulation techniques with traditional structural biology, and Stockholm University has very high expertise in both of these fields,” says David Drew from the Department of Biochemistry and Biophysics.

Large research grant from the Knut and Alice Wallenberg Foundation

A new research grant worth SEK 29 million from the Knut and Alice Wallenberg Foundation to David Drew and Stockholm University will make it possible to take the research on membrane-bound proteins a step further. David Drew will, together with Erik Lindahl, Arne Elofsson, and Jan-Willem de Gier, each of whom leads a research team at Stockholm University’s Center for Biomembrane Research (CBR), combine the knowledge of the four teams in order to determine the structure and function of the human varieties of membrane-bound proteins. The goal of the project “Structural dynamics and allosteric regulation of mammalian channels and transporters” is to go from simple models of bacterial proteins to understanding how human membrane proteins work as transporters and ion channels, as well as how other molecules – such as medicine – control their function.

Sodium ions may enter a cell through a lift-like mechanism as shown in the picture.  This knowledge could have major implications for the understanding of how cells work, as well as for the development of new cancer medicine. It is for the development of this research that David Drew has received his grant.

Sodium ions may enter a cell through a lift-like mechanism as shown in the picture. This knowledge could have major implications for the understanding of how cells work, as well as for the development of new cancer medicine. It is for the development of this research that David Drew has received his grant.
 

Several grants to Stockholm University

Research on membrane proteins and protein structure determination at Stockholm University is strengthened further by several large grants to Professor Gunnar von Heijne at the Department of Biochemistry and Biophysics. He has been granted a total sum of SEK 66 million (31 million each from the Knut and Alice Wallenberg Foundation and the Erling-Persson Family Foundation, as well as 4 million annually from SciLifeLab) for a new laboratory for protein structure determination at SciLifeLab. The four research teams mentioned above, and a world-leading research team from Munich, are among those who will conduct their research in this laboratory.