Citations 2
Structural insight into the CUB2 domain’s role in enteropeptidase-mediated trypsinogen activation
Song, Qiuyue, Peng, Lisi , Yang, Xia , Xu, Jiaheng , Zhang, Deyu , Tian, Xiaorong, Li, Shiyu , Ji, Baoan , Jin, Zhendong, Ding, Zhanyu , Li, Zhaoshen , Huang, Haojie, Huang, Haojie , Song, Qiuyue , Li, Shiyu, Zhang, Yu , Li, Zhaoshen , Huang, Haojie
Proceedings of the National Academy of Sciences | March 16, 2026 | Volume: 123 | Issue: 12 | Pages: No page available
Elucidating the structure and function of enteropeptidase (EP) is essential for advancing our understanding of its biological significance, particularly in regulating trypsinogen activation. Using cryo-EM and enzymatic activity, we uncovered the significance of the CUB2 domain in mediating the cleavage of macromolecular substrates. We identified crucial binding loops and key residues for EP’s proteolytic function. The mutation E574A enhanced the proteolytic activity of EP, whereas the mutation N619A diminished its cleavage efficiency, highlighting the importance of surface-charged interactions in modulating EP’s activity. A proteolytic cycle was proposed to deepen our understanding of the trypsinogen activation by EP. This work offers valuable insights into the molecular mechanisms underlying EP’s interaction with its substrate, and opens up avenues for therapeutically modulating EP-mediated proteolysis.
Unraveling the Microenvironment and the Pathogenic Axis of HIF‐1α–Visfatin–Fibrosis in Autoimmune Pancreatitis Using a Single‐Cell Atlas
Zhang, Deyu , Ma, Congjia , Liu, Yanfang , Liu, Zaoqu, Li, Wanshun , Liu, Yue , Wu, Chang , Sun, Liqi , Jiang, Fei , Jiang, Hui , Su, Xiaoju, Peng, Lisi , Wang, Xinyue , Yin, Hua, Wan, Dongling, Zhou, Yuyan , Tian, Xiaorong , Li, Shiyu , Jin, Zhendong , Ji, Baoan , Li, Zhaoshen , Huang, Haojie , Wang, Zhen , Huang, Haojie , Wang, Zhen , Li, Jiayu , Li, Zhaoshen
Advanced Science | January 31, 2025 | Volume: 12 | Issue: 12 | Pages: No page available
AbstractAutoimmune pancreatitis (AIP) is identified as a severe chronic immune‐related disorder in pancreas, including two subtypes. In this study, pancreatic lesions in patients diagnosed as either type 1 AIP or type 2 AIP are examined, and these patients’ peripheral blood at single‐cell level. Furthermore, flow cytometry, immunofluorescence, and functional assays are performed to verify the identified cell subtypes. In type 1 AIP, there is a notable increase in the amount of B cells and plasma cells, and IgG4+ plasma cells are key pathogenic cells of AIP. The differentiation path of naïve‐stage B cells into IgG4+ produced plasma cells is observed, and an increased amount of T helper cells and T follicular helper (Tfh) cells. This study also reveals that HIF‐1α, an activated transcriptional factor, can directly bind to promoter site of NAMPT, promoting higher levels of visfatin production in HIF1A+ classical monocytes. Pancreatic stellate cells can be activated by extracellular visfatin and promote the development of fibrotic response in pancreatic lesions across both AIP subtypes. The current findings shed light on the exploration of dynamic alterations in peripheral blood cells and cell subgroups in pancreatic lesions of AIP, while elucidating a pathogenic cell subset and potential fibrosis mechanism of AIP.