Recovery and Response of Crohn's Associated Mutants to Bacterial Cell Wall Fragments

• DOI: 10.1096/fasebj.29.1_supplement.571.25
• Publication Date: 2021-06-21T18:21:38Z
• Authors: Amy Schaefer; James Melnyk; Vishnu Mohanan; Catherine Grimes
• Keywords: Muramyl dipeptide

The objective of this study is to determine the activity and binding capabilities Crohn's associated mutant Nod2 protein. disease a debilitating inflammatory bowel alleged be caused by genetic factors malfunctioning immune system. A susceptibility gene has been identified on chromosome 16 that responsible for encoding nucleotide‐binding oligomerization domain‐containing protein 2 (Nod2). an innate receptor responds bacterial cell wall fragments initiate NF‐κB pathway. Three specific mutations have implicated in increased disease. These prevent it from recognizing or responding its proposed ligand, muramyl dipeptide (MDP), fragment. Our lab shown Crohn's‐associated mutants suffer stability issue; however, are able rescued with use chaperone Upon stabilization these mutants, assays studies can help elucidate information about where fail perform, MDP signaling activation. Luciferase reporter surface plasmon resonance were optimized Nod2/MDP interaction. In presence tag, activation was there no evidence diminished MDP. This suggests root cause misregulation due one issue folding rather than inability bind signal.