Nature：徐华强/马雄团队解析Ostα/β结构，破解胆汁酸转运关键机制

Core Viewpoint - The article discusses the critical role of bile acids in digestion, energy metabolism, and hormone signaling, highlighting the importance of the Ostα/β transport protein in the enterohepatic circulation of bile acids and its unique transport mechanism [2][3][11]. Group 1: Research Findings - A research team from the Shanghai Institute of Materia Medica and affiliated hospitals published a study in Nature revealing the unique structure and transport mechanism of the Ostα/β protein [3]. - The study utilized cryo-electron microscopy, molecular dynamics simulations, and electrophysiological analysis to elucidate the three-dimensional structure and substrate recognition patterns of Ostα/β [3][4]. - The Ostα/β complex was successfully expressed and purified, showing a symmetric tetrameric assembly with a novel seven-transmembrane helix folding pattern [4]. Group 2: Mechanism of Action - The structural analysis identified a substrate-binding groove near the cytoplasmic side of the membrane, which is modified by palmitoylation, creating a microenvironment suitable for binding amphipathic steroid molecules [5]. - The research demonstrated that Ostα/β interacts with physiological substrates, such as taurocholic acid and dehydroepiandrosterone sulfate, through specific electrostatic interactions [5]. - A hydrophilic channel extending from the binding groove to the extracellular side was identified, suggesting a pathway for substrate translocation across the membrane [5]. Group 3: Physiological Implications - The study introduced a novel method to monitor bile acid transport in real-time using whole-cell patch-clamp techniques, demonstrating that the transport direction of Ostα/β is influenced by the electrochemical gradient across the membrane [8][9]. - The findings indicate that membrane potential is a key regulatory factor that biases the transport direction, enhancing the understanding of bile acid excretion under different physiological conditions [9]. Group 4: Clinical Relevance - The research fills a critical gap in understanding bile acid excretion in the enterohepatic circulation, providing insights for potential therapeutic interventions in liver and biliary diseases [11]. - Dysregulation of bile acid metabolism is linked to various liver diseases, and targeting Ostα/β could offer a direct approach to modulate bile acid distribution and alleviate related pathologies [11]. - The structural comparison suggests that Ostα/β may belong to a new class of transport proteins, opening new avenues for research on the TMEM184 protein family and its potential disease associations [11].