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Sodium-taurocholate Co-transporting Polypeptide

spinqualitylabelsall models Sodium-taurocholate co-transporting Polypeptide (NTCP) 7PQQ Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Introduction Sodium-taurocholate Co-transporting Polypeptide (NTCP) is found within the membrane of hepatocyte, and its primary role is to facilitate the transport of bile salts into hepatocytes from the bloodstream. This is important because 90% of human bile salts are recycled daily, so the function of NTCP is critical in providing bile salts to solubilize fats for digestion. In addition to transporting bile salts into the cytoplasm of hepatocytes, NTCP also serves as a receptor for Hepatitis B (HBV) and Hepatitis D (HDV) viruses. Structure Significant Residues The vast majority of residues involved in bile salt uptake are also involved in HBV/HDV infection. Residues 84-87 of Human NTCP have been shown to be vital for preS1 domain recognition along with bile salt uptake. Residues 157-165 (INSERT GREEN LINK) have also been shown to be vital for preS1 recognition and bile salt uptake. Altering residues in either of these two sections hinders preS1 binding and therefore HBV/HDV infection. However, these mutations also prevent bile salt uptake. Molecular Mechanism Mechanism of Bile Salt Uptake NTCP Open-Pore State Mechanism of HBV/HDV Infection HBV/HDV infection is reliant on multiple properties that must be present on both the virus itself and the NTCP protein. First, the HBV/HDV capsid must be myristoylated in order for proper recognition by NTCP. Residues 2-48 are the most significant residues of HBV/HDV that are highly conserved amongst these viruses that are vital for infection. Specifically, residues 8-17 on HBV/HDV have been identified as the most important. These residues are NPLGFFPDHQ. There are two proposed mechanisms as to how exactly HBV/HDV bind to NTCP and enter the cell. In both mechanisms, there is an initial translocation of the myristoylated preS1 HBV/HDV virus to interact with the host cell (hepatocyte). The first mechanism involves the myristoyl group of preS1 binding to the host cell membrane, not NTCP, and residues P8-H17 interacting with NTCP residues 157-165. The second mechanism involves the myristoyl group of preS1 binding directly into the open-pore of NTCP interacting with residues 157-165. In both proposed mechanisms, the interactions with the extracellular residues 84-87 of NTCP is unknown. Relevance This is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

Student Contributors

Ben Minor Maggie Samm Zac Stanley