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Structure of key molecule in immune system provides clues for designing drugs
Date:12/27/2010

PHILADELPHIA - A team from the University of Pennsylvania School of Medicine and Utrecht University has deciphered a key step in an evolutionarily old branch of the immune response. This system, called complement, comprises a network of proteins that "complement" the work of antibodies in destroying foreign invaders. It serves as a rapid defense mechanism in most species from primitive sponges to humans.

In a study published in the December 24 issue of Science, the groups of John Lambris, PhD, the Dr. Ralph and Sally Weaver Professor of Research Medicine at Penn, and Piet Gros at Utrecht, detail the atomic structure of two key transient enzyme complexes in the human complement system.

Complement proteins mark both bacterial and dying host cells for elimination by the body's cellular cleanup services and have been implicated in at least 30 diseases, including stroke, myocardial infarction, and age-related macular degeneration. The findings, Lambris says, provide a molecular scaffold for designing novel drug therapeutics.

"Now we will be able to design specific complement inhibitors to target this complex and in that way inhibit activation of the complement cascade, because now we know which parts of the proteins are essential for activity," Lambris says.

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The complement system is a form of "innate," or generic immunity, unlike "adaptive" immune responses, in which cellular mediators such as B and T cells learn to target specific antigens through recognition by either antibodies or cell receptors. The complement process unfolds as a complex biochemical network of molecular and cellular communication events, which result in the destruction and elimination of pathogens and damaged cells and eventual recruitment of immune cells.

The two enzyme complexes Lambris studied, called C3bB and C3bBD, drive a central step in amplifying the response by complement proteins. In that step, t
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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