Elucidation of the interactome for the bioactive disaccharide Man(B1-4)GlcNAc

PROJECT SUMMARY Some autoimmune diseases, including systemic lupus erythematosus or “lupus,” are now known to occur because of the pathogenic excess of an intracellular disaccharide called Man(b1- 4)GlcNAc. The accumulation of this disaccharide in cells can lead to the erroneous activation of immune responses, leading to autoimmunity. The molecular mechanisms through which Man(b1- 4)GlcNAc regulate autoimmunity remain unknown, due to the difficulties of capturing the intracellular interactors and receptors of free oligosaccharides, like Man(b1-4)GlcNAc. We will use a chemoproteomic mass spectrometry-based approach to elucidate the interactome of Man(b1-4)GlcNAc to identify its functional receptors. The accomplishments resulting from this work will result in an enhanced understanding of aberrant glycosylation and the bioactivity of free Man(b1-4)GlcNAc, as well as pave the pathway for studying the interactomes of intracellular free oligosaccharides.