Sandbox Reserved 1769

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 a transmembrane protein found in hepatocytes, and its primary role is to facilitate the transport of bile salts into hepatocytes from the bloodstream. 90% of human bile salts are recycled daily, so the function of NTCP is critical in providing bile salts to solubilize fats for digestion. NTCP also serves as a receptor for Hepatitis B (HBV) and Hepatitis D (HDV) viruses. Structure Structures were determined by cryogenic electron microscopy (Cryo-EM) of NTCP in complex with antibodies or nanobodies, revealing two key conformations in NTCP's transport mechanism. There are nine transmembrane alpha helices traversing the plasma membrane, with the N-terminus located on the extracellular side of the plasma membrane and the C-terminus located on the intracellular side. The panel domain is formed by transmembrane helices TM1, TM5, and TM6. The core domain is formed by the packing of a helix bundle consisting of TM2, TM3, and TM4 with another helix bundle consisting of TM7, TM8, and TM9. The two helix bundles are related by pseudo two-fold symmetry. Transmembrane helices are connected by short loops as well as extracellular and intracellular alpha helices that lie nearly parallel to the membrane. Domains NTCP contains two characteristic domains, the core and panel domains. Movement of these two domains characterizes the two known conformational states implied in bile salt uptake. Panel Domain: 1-44, 155-208 Core domain: 45-154, 209-309 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. Function Mechanism of Bile Salt Uptake NTCP Open-Pore State Inward Facing 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 (INSERT BLUE LINK) 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