PETRA III Science Seminar | Structural and Functional Insight into the N-glycosylated Human Protein Zonulin, a Therapeutic Target for Celiac Disease

by Jialing Song (University of Science and Technology of China)

Tuesday 26 Sept 2023, 02:15 → 03:00 Europe/Berlin

Virtual

Celiac disease (CeD) is defined as an autoimmune disease triggered by undigested gluten, which can occur at any age and affect 1 person in every 100. Currently there is no cure or medication available and the only option for treatment is a life-long gluten-free diet. The zonulin-medicated modulation of paracellular transport for undigested gluten is considered as a pivotal step in pathogenesis of CeD. Recently, a small molecule inhibitor, Larazotide (AT1001) has been developed, acting as zonulin antagonist that blocks the zonulin signal pathway of CeD and it is currently in the phase III clinical trials. Although the zonulin is identified as pre-PH2 by molecular techniques and MS, there is lack of much more structural and biophysical characterization of zonulin as molecular structural basis for drug development. Besides, the AT1001, which is shown to have inhibition effect on the zonulin signal pathway, but without evidence of interaction with zonulin. This talk presents structural and biophysical insight into human recombinant zonulin, especially the native oligomeric state with multiple methods. Furthermore, in this talk I will show results on the functional characterization of recombinant zonulin oligomers interaction with the small molecular inhibitor AT1001.