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. Bile salts are derived from cholesterol, and they serve an important role in the mechanical digestion of fats and ultimately facilitate the chemical digestion of lipids. Their mixture of hydrophobic and hydrophilic regions allow them to act as a bridge between aqueous and lipid environments. In the small intestine, bile salts emulsify fats and cholesterol into micelles. Without bile, fats would spontaneously separate out of the aqueous mixture in the duodenum and would not be accessible to pancreatic lipase to break down fat in your diet. Proper fat digestion requires both pancreatic lipase and bile, so the working transport of bile salts through NTCP in necessary to facilitate this action. 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.

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Function

Bile Salt Uptake

HBV/HDV Infection

Structure

Structures were determined by cryogenic electron microscopy (Cryo-EM) of NTCP in complex with antibodies or nanobodies that stabilize both of these conformations. 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.

Proline/Glycine Hinge

Core & Panel Domains

Sodium Binding Sites

Significant Residues

Molecular Mechanism

Mechanism of Bile Salt Uptake

Mechanism of HBV/HDV Infection

Medical Relevance

Relevance

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