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Molecular structure key to allergies and asthma is identified

EVANSTON, Ill. -- In a breakthrough that could affect the more than 50 million Americans who suffer from allergies and asthma, researchers at Northwestern University and Harvard Medical School have identified the structure of the interaction complex of two molecules that are central to the allergic response in humans.

The discovery of how the antibody binds to the mast cell receptor could lead to the development of a new class of drugs that attack allergies at their source, preventing the cascade of released chemicals that leads to the itching, sneezing and congestion of allergies, the life-threatening respiratory distress of asthma and anaphylactic shock. Todays commercial drugs only treat symptoms once the allergic response is already under way.

The findings, which will be published July 20 in the journal Nature, also may lead to novel treatments for autoimmune disorders and improved cancer therapies based on antibodies.

The researchers determined the structure by imaging crystals of the molecular complex of the antibody immunoglobin-E (IgE) and its high-affinity receptor, using the extremely brilliant X-rays produced by the Advanced Photon Source (APS) synchrotron at Argonne National Laboratory in Illinois.

"In order to design drugs effectively, a chemist needs to know the structure and shape of the target molecules," said Theodore S. Jardetzky, the Northwestern X-ray crystallographer who led the study. "Our discovery provides a three-dimensional image of how the two molecules interact, showing where and how the antibody binds to the receptor. This is valuable information in the world of drug design."

Antibodies in the human immune system act as antennas for antigens, molecules foreign to the body, and attach to antibody receptors on the surface of immune system cells. When antigens are detected, the antibodies activate the cells. Once triggered, the cells respond by unleashing a barrage of immune system defense mechanisms.


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Contact: Megan Fellman
fellman@northwestern.edu
847-491-3115
Northwestern University
18-Jul-2000


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