Multistep receptor binding of the hepatitis B virus preS1 domain.

ABSTRACT: The preS1 domain present on hepatitis B and D virus particles is an intrinsically disordered peptide (IDP) essential for recognizing the host receptor, sodium taurocholate co-transporting polypeptide (NTCP). However, it remains poorly understood how the disordered preS1 peptide achieves high-affinity binding through its conformational change. Here, we reveal a stepwise binding process through which multiple regions within preS1 cooperate to establish the stable binding to NTCP. By combining structure-based molecular simulations with virological assays, we show that Asn9^preS1, Gly12^preS1, and His17^preS1 primarily mediate the NTCP binding by forming a tandem loop core structure that docks into the bile acid tunnel of NTCP, creating an extensive binding interf

SUBMITTER: Kobayashi C 

PROVIDER: S-EPMC12858840 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature