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Background

Structural Overview

Binding Pocket

Confirmation Change

Mechanism

The NTCP protein goes through a conformational change when assisting in the uptake of bile salt into the cell. This is accomplished through the opening of a wide transmembrane pore, creating a transport pathway for bile salts. The mechanism includes two sodium metal ions that allow for residue stabilization when going through the conformational change. Binding of the preS1 region of the HBV/HDV virus blocks any subsequent bile salt uptake. Thus, preS1 binding blocks the conformational change and entry of any salts into the cell. Residues 8-17 of preS1 are critical for NTCP:pres1 binding. Patch 1 and Patch 2 (external) residues interact with residues 8-17 of preS1 to facilitate binding.

Figure 1. Bile Salt Uptake Mechanism.

Function

Significance

NTCP serves a multitude of biological functions, including bile salt uptake and HBV/HDV binding.

Bile Salt Uptake

Figure 2. Bile Salt Structure.

HBV/HDV

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