Key protein opens door to new treatments

It is known that a key protein in the immune system, C3, bonds with and interacts with up to 40 other proteins and receptors in the blood. But until now it has not been understood what the significance of these bonds might be. In the latest issue of the scientific journal Nature a Swedish-Dutch research team has laid bare the crystal structure of the protein, which may lead to tailor-made treatments for autoimmune diseases.

Scientists at Uppsala University, in collaboration with the universities of Utrecht and Leiden in the Netherlands and Kalmar in Sweden have managed to describe the crystal structure of one of the key proteins in the natural immune system, complement factor C3. This protein was isolated and characterized for the first time here at Uppsala University more than 40 years ago. A large number of studies have shown since then that the protein bonds with and interacts with 30-40 other proteins and receptors in the blood and on white corpuscles. But despite repeated attempts, it had not been possible to determine its crystal structure, and this has hampered our understanding of these bonds.

– The protein is of great importance to the body’s defense against micro-organisms and is one of the main factors in the inflammatory process in many autoimmune disorders,says Bo Nilsson, Department of Clinical Immunology, who directs the research team.

The three dimensional structure now shows that the protein developed from a proto-protein about 800 million years ago and that this protein has since given rise to several other defense proteins in organisms from insects to mammals. The structure also shows that the protein undergoes a drastic metamorphosis after it has become activated, which will explain how the interplay with other proteins is regulated. The new findings may lead to tailor-made drugs to regulate the destructive inflammatory processes that are associated with autoimmune diseases like arthritic rheumatism, SLE, vascular inflammations, hemolytic anemias, kidney inflammations, and blood poisoning.