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Chain reaction in the human immune system trapped in crystals
Date:9/11/2012

The complement system is part of the innate immune system and is composed of about 40 different proteins that work together to defend the body against disease-causing microorganisms. The complement system perceives danger signals in the body by recognising characteristic molecular patterns presented by pathogenic microorganisms or some of our own sick or dying cells that must be eliminated.

The complement system can be found in the blood, but also in the fluid surrounding the cells in tissues. Complement serves as the first line of defence against many pathogenic organisms, and its recognition of danger signals is handled by specialised proteins in the complement system.

For more than 20 years, Professor Steffen Thiel at the Department of Biomedicine, Aarhus University, has been a world leader in studies of MBL and MASP-2, which are two key proteins in the complement system. When MBL recognises the danger signal, MASP-2 is converted into an active enzyme that can now cleave the protein C4, a third important protein in the complement system. This cleavage is the first step in a chain reaction that ends with the elimination of pathogenic bacteria and dying cells. A research team led by Associate Professor Gregers R. Andersen at the Department of Molecular Biology and Genetics, Aarhus University, has now in collaboration with Professor Thiel succeeded in determining in atomic detail how the active enzyme MASP-2 recognises the substrate C4.

Crystals shot with X-rays

Two PhD students in molecular biology, Rune T. Kidmose and Nick S. Laursen, isolated the protein C4 from blood plasma, whereas they obtained the MASP-2 from Hungarian colleagues. They then crystallised the substrate C4 alone, but to their surprise they could also crystallise the enzyme-substrate complex C4MASP-2. By exposing the resulting crystals to intense X-ray radiation, the two students managed within a year to determine the atomic structures of the C
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Contact: Gregers Rom Andersen
gra@mb.au.dk
45-87-15-55-07
Aarhus University
Source:Eurekalert  

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Chain reaction in the human immune system trapped in crystals
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