Zhejiang University Co-authored letter revealing key protein modifications behind intestinal diseases

Inflammatory bowel disease is the general name for several intestinal diseases, the most well known being Crohn's disease and ulcerative colitisThe number of patients suffering from these diseases is not very large, and there will be diarrhea, blood and other symptoms, serious cause of physical discomfortIn the long-term onset, it also carries the risk of worsening colorectal cancercurrently, scientists believe inflammatory bowel disease is linked to the body's immune functionAmong them, NOD1 and NOD2 proteins play an important role in the immune response of the intestinesAs a type of protein receptor, they are able to identify metabolites secreted by microorganisms, which arouse the immune response of the gut to fight infectionAnd once NOD1/2 mutates and becomes dysfunctional, it can cause severe immune diseases and inflammatory responsesprevious, scientists have discovered many mutations in the NOD1 and NOD2 proteins and found a link between them and inflammatory bowel diseaseHowever, there has been no detailed answer to why these mutations cause diseaseThis is the highlight of this paperinhibit s-palm amide of NOD1/2 (Figure B), affecting their normal membrane positioning (Image Source: 1)First, the team found that NOD1 and NOD2 would be "S-palmiation" modificationsBy adding specific lipid molecules to the protein, this modification can alter the intracellular positioning of the proteinIf this modification is inhibited, the NOD1/2 protein will lose normal cell membrane positioning, distributed in the cytoplasmThis is similar to the positioning of the mutated NOD1/2 proteinSubsequent studies have also shown that S-palm amide modification is essential for normal cell location and function of NOD1/2So, what enzyme catalyzes the S-palm amide modification of NOD1/2? The researchers screened the protein that interacted with NOD1/2 and found a protein called ZDHHC5 It not only has the same cell location with NOD1/2, but also inhibits its expression through RNA interference, which can affect the modification of NOD1/2 and cause disorders in its cell location Combining these results, the researchers note in their paper that ZDHHC5 mediates post-retroviral modification of NOD1/2 and can affect its positioning and function inhibits the expression of the ZDHHC5 protein, it will affect the positioning of the NOD1 protein (Photo Source: Resources 1) it is worth noting that in many inflammatory bowel diseases, the mutated NOD2 protein, its S-palm amide modification, will have a severe reduction, the range of up to 70%-90% The study, published in Science, explains molecular mechanisms that cannot be properly located on the cell membrane, affecting their ability to regulate immune responses and causing disease " our findings point to the potential importance of palm-based embellishment modifications Too much or too little can affect the inflammatory response," said Professor Gregory D Fairn, one of the authors of the study "