Hope for Treating Diseases Via Two Structures Found in Old Immune System

Insight into how the body fights invading microbes while avoiding attacking itself have been provided courtesy two new structures belonging to the oldest branch of the human immune system.

Both structures involve a central component of an enzyme important to the complement system of the immune response.

The structures may pave the way to more efficient therapeutics for such complement-mediated diseases as age-related macular degeneration, rheumatoid arthritis, or systemic lupus erythematosus and give insight into the pathogenesis of other immune and inflammatory diseases.

The complement system, an evolutionarily old arm of the immune system, comprises a network of proteins that "complement" the work of antibodies in destroying foreign invaders.

When complement proteins are triggered into action by a microbe, the proteins ultimately form a complex enzyme called C3 convertase, which triggers a cascade of immune and inflammatory reactions.

In order to avoid self-attack, regulatory proteins like factor H bind with C3b, a central component of C3, to help the immune system recognize the body's own tissue and keep complement in check.

Researchers at the University of Pennsylvania School of Medicine, in collaboration with colleagues at Utrecht University in the Netherlands, have determined the structure of C3 convertase and of the C3b fragment in complex with factor H.

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"Research on the complement system has waited more than 30 years for these structures," Nature magazine quoted senior author Dr. John Lambris as saying.

He added: "This gives us a structural model for designing new therapies for several immune-mediated diseases."

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The findings have been published in two companion papers in Nature Immunology.

Source-ANI
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