Decade-year old structure incorrect
3 Jun 2011 by Evoluted New Media
A decade-year old structure of an important complex in the human immune system has shown to be incorrect by two researchers, who hope to use their new structure to design treatments for autoimmune diseases.
A decade-year old structure of an important complex in the human immune system has shown to be incorrect by two researchers, who hope to use their new structure to design treatments for autoimmune diseases.
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The molecular structure of the CR2-C3d complex shown as a ribbon diagram |
Dr Jean van den Elsen and Dr David Isenman have been studying the complex for ten years – ever since it’s atomic structure was published – but decided to reanalyse the structure to develop a correct understanding of its atomic details.
“The new structure is very different to the previous one, but its features conform to all existing biochemical data,” said van den Elsen, from the University of Bath.
They focused on the protein C3 – from the complement system, part of our innate immune system present since birth – and it’s molecular partner complement receptor 2 (CR2). CR2 is found on the surface of B cells, the antibody producing cells of the adaptive immune system.
C3 breaks down to produce C3d when attached to a pathogenic antigen, and acts as a bridge between the innate and adaptive immune system by connecting the antigen recognition entity of the B cell with the complement receptor. This increases the production of antibodies which attack the pathogen.
The C3d-CR2 interaction increases the sensitivity at which a pathogen is recognised and reacted to in the body which is essential to keeping us healthy from disease. This has important implications for the design of new vaccines against diseases cause by microbial pathogens.
However, this can go wrong in autoimmune diseases when the immune system mistakes part of the body as a pathogen and attacks it.
“To treat antibody-mediated autoimmune disease there is a potential to target the ‘bridging’ action of C3d with CR2, through designing drugs that would inhibit the interaction,” said Isenman from the University of Toronto. “However, due to the misunderstandings caused by the previous structure of the complex, over the past ten years progress in this field has been delayed.”
The scientists hope to use the new structure as a platform to design inhibitory compounds that may be useful in treating antibody-mediated autoimmune disease such as Multiple Sclerosis and SLE.
