Approximately 30 per cent of all proteins in a typical cell are integrated into the cell’s lipid membranes. These so-called “membrane proteins” perform a variety of important functions in the cell: they are responsible for transporting ions, molecules, and macromolecules into and out of the cell; they relay signals between the cell’s external and internal environments; and they physically interact with nearby cells. Furthermore, membrane-bound enzymes manage important parts of the cell’s metabolism.

In spite of their many important functions, our biochemical knowledge of membrane proteins is, in many respects, insufficient and far behind our knowledge of water-soluble proteins. This is due to the fact that membrane proteins are much more difficult to purify and handle biochemically than water-soluble proteins.

Membrane protein
Membrane protein

The currently dominant method for determining the three-dimensional structure of proteins at the atomic level is x-ray crystallography. However, structural biology studies of membrane proteins using this method often fail, as the researchers are unable to obtain usable crystals.

Development of alternative methods

Parallel to the rise of x-ray crystallography in recent years, there has been a dramatic development of an alternative method for determining the structure of proteins and protein complexes based on electron microscopy instead of x-rays. This so-called “single-particle cryo-EM” (SP-CEM) technique does not require protein crystals. Instead, it is based on the imaging of thousands of individual protein molecules in an electron microscope and the computational alignment of the images into a three-dimensional structure model.

SEK 31 million from the Knut and Alice Wallenberg Foundation

Sweden has a very strong international position in membrane protein research, but lacks the necessary expertise in high-resolution SP-CEM.  Now, however, the work to develop this new method has received a large grant. The Knut and Alice Wallenberg Foundation has awarded SEK 31 million to Professor Gunnar von Heijne, Department of Biochemistry and Biophysics, Stockholm University, for the research project “Single-particle cryo-EM studies of membrane protein biogenesis and structure”.

The project is a collaboration between four research teams at Stockholm University’s Center for Biomembrane Research (CBR) and a research team from Munich that is world-leading in the field. The new laboratory will also function as a national resource within SciLifeLab.

Large grant from the Erling-Persson Family Foundation

Gunnar von Heijne was also recently awarded additional funding for the same project from the Erling-Persson Family Foundation (SEK 31 million) and SciLifeLab (SEK 4 million per year).

“A better understanding of how the cell produces proteins, and what the three-dimensional structure of the proteins looks like, will provide an important basis for future basic research in biology, as well as for the development of medicine.  Membrane-bound proteins are particularly important objects of study, as it is estimated that half of all pharmaceutical drugs target membrane proteins,” says Gunnar von Heijne.

Membrane protein Gunnar von Heijne (Photo: Eva Dalin).
Gunnar von Heijne (Photo: Eva Dalin).

Another SEK 68 million to infrastructure

The Knut and Alice Wallenberg Foundation has also granted Gunnar von Heijne, along with Siv Andersson from Uppsala University, an infrastructure grant worth SEK 68 million, which will allow for an extension of the Wallenberg Advanced Bioinformatics Infrastructure (WABI) at SciLifeLab. WABI, through SciLifeLab, provides bioinformatics support to Swedish researchers. The extension of this funding until 2020 will also allow for an increase in the number of bioinformaticians.

SciLifeLab – national centre for molecular biosciences

SciLifeLab is a national centre for molecular biosciences with a focus on health and environmental research. The centre is a collaboration between Karolinska Institutet, KTH Royal Institute of Technology, Stockholm University, and Uppsala University.