University of Delaware researchers have identified a protein, hiding in plain sight, that acts like a bodyguard to help protect and stabilize another key protein, that when unstable, is involved in Crohn's disease. The fundamental research points to a possible pathway for developing an effective therapy for the inflammatory bowel disease.
The research, by Catherine Leimkuhler Grimes, assistant professor of chemistry and biochemistry at UD, and Vishnu Mohanan, doctoral student in biological sciences, is published in the July 4 issue of the Journal of Biological Chemistry. The study was funded by a grant from the National Institutes of Health (NIH). As the scientists point out, our immune system provides the first line of defense against invading pathogens, a task even more challenging in the human gut, where over a trillion commensal bacteria live resident microorganisms that help convert food into protein, vitamins and minerals.
To distinguish "bad" versus "good" bacteria, our bodies rely on a complex network of receptors that can sense patterns that are unique to bacteria, such as small fragments of bacterial cell wall. The receptors recognize and bind to these fragments, triggering an immune response to take out the "bad guys" or control the growth of the "good guys."
However, when one of these receptors breaks down, or mutates, an abnormal immune response can occur, causing the body to mount an immune response against the "good" bacteria. Chronic inflammatory disorders, such as Crohn's disease, are hypothesized to arise as a result.
The UD team focused on a protein called NOD2 nucleotide-binding oligomerization domain containing protein 2. More than 58 mutations in the NOD2 gene have been linked with various diseases, and 80 percent of these mutations are connected specifically to Crohn's disease, according to Grimes.
In experiments to unveil NOD2's signaling mechanisms and where they break do
|Contact: Donna O'Brien|
University of Delaware