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.
Function
Bile Salt Uptake
HBV/HDV Infection
Structure
Proline/Glycine Hinge
Core & Panel Domains
Sodium Binding Sites
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 (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.
Medical Relevance
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.
