Structural mapping of NTCP distinguishes its dual functionality as a hepatitis B virus receptor and bile acid transporter.

ABSTRACT: Sodium taurocholate cotransporting polypeptide (NTCP) is a hepatic transmembrane (TM) protein that functions both as a bile acid transporter and as a host receptor for hepatitis B and D viruses via the viral preS1 binding. The structural and mechanistical determinants for NTCP's dual functions remain largely undefined. In this study, using comprehensive structure-guided alanine-scanning mutagenesis based on the cryo-electron microscopy structure of the preS1/NTCP complex, we identified 13, 8 and 9 NTCP amino acid residues critical for viral infection, preS1 binding, and bile acid transport, respectively. Key residues overlappingly regulating viral receptor and transporter functions were located primarily at TM1 and TM8, whereas TM5 and outer-surface NTCP loops mediated viral receptor-speci

SUBMITTER: Matsuzawa K 

PROVIDER: S-EPMC12810916 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature