On September 26, Prof. Yu Ye from School of Basic Medical Sciences and Clinical Pharmacy and National Key Laboratory of Multi-target Natural Drugs, in collaboration with Shanghai Jiao Tong University School of Medicine, published a long article entitled Structural basis for inositol pyrophosphate gating of the phosphate channel XPR1 online in Science as First Release. Prof. Yu Ye is the co-corresponding author, Dr. Yue Chenxi from the School of Basic Medicine and Clinical Pharmacy is the co-first author, and China Pharmaceutical University (CPU) is the co-corresponding author of the paper.
Phosphorus is an important element that constitutes life and plays various roles in life activities, and XPR1 is the only transporter protein found to have the function of exocytosis phosphate. This study combines structural biology and electrophysiology to comprehensively analyze the structure, function, and regulatory mechanism of human XPR1 (Figure 1), revealing the basic structural and functional features of XPR1 as an inositol pyrophosphate-gated phosphate channel and elucidating the mechanism by which inositol pyrophosphate activates XPR1 through dual binding and regulates the inorganic phosphate current. Inositol activates XPR1 through dual binding and regulates the inorganic phosphate current (Figure 2). This discovery provides an important basis for understanding the transmembrane transport of phosphate and its regulatory mechanism, and opens new research directions for the diagnosis of related diseases and the development of therapeutic drugs.
Figure 1. inorganic phosphate (Pi) exocytosis structure and its corresponding workings mediated by pyrophosphatidylinositol (PP-IPs) versus phosphatidylinositol (IPs) for XPR1 activation.
Figure 2. Inorganic phosphate flow generated by activation of XPR1 by pyrophosphatidylinositols (PP-IPs) and phosphatidylinositols (IPs) has typical ion channel characteristics.
Original Link：https://doi.org/10.1126/science.adp3252
