Core Viewpoint - The research reveals the high-resolution structure and transport mechanism of the OSTα/β protein, a key bile acid transporter, providing insights into its unique assembly and function, which could lead to new therapeutic strategies for related diseases [3][6][8]. Research Background - The OSTα/β protein is crucial for the enterohepatic circulation of bile acids, facilitating the reabsorption of bile acids from intestinal cells back into the bloodstream [5][9]. - Abnormal function of OSTα/β can lead to digestive disorders, cholestasis, and liver damage, highlighting its importance in hormone regulation and lipid metabolism [5][9]. Key Findings - The study successfully elucidates the high-resolution three-dimensional structure of the OSTα/β complex, identifying it as a heterotetramer composed of two OSTα and two OSTβ subunits, which ensures stability through tight inter-subunit interactions [6][8]. - A novel "sliding" transport model is proposed, differing from traditional "alternating access" models, allowing bile acids to move through a semi-embedded membrane channel without significant conformational changes [6][8]. Significance - This unique transport mechanism distinguishes OSTα/β from other known bile acid transport proteins, representing a previously unknown substrate transport mechanism within the solute carrier protein superfamily [8]. - The findings provide a new structural framework for understanding bile acid transmembrane transport and lay a solid theoretical foundation for the development of targeted drugs against OSTα/β [8]. - Potential drug development strategies include creating agonists to enhance function and specific inhibitors for treating cholestasis [8].