Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2025

Structural basis of the hepatitis B virus X protein in complex with DDB1

Joao Diogo Dias
Basile Jay
Shunsuke Kita
Hiroyuki Takeda
Naoki Kishimoto
Shunsuke Sasaki
  • Fonction : Auteur
  • PersonId : 1307138
  • IdHAL : sasaki-imn
Shogo Misumi
Christine Neuveut
Takashi Sumikama
Mikihiro Shibata
Katsumi Maenaka

Résumé

A cure for chronic hepatitis B requires eliminating or permanently silencing covalently closed circular DNA (cccDNA). A pivotal target of this approach is the hepatitis B virus (HBV) X protein (HBx), which is a key factor that promotes transcription from cccDNA. However, the HBx structure remains unsolved. Here, we present the cryoelectron microscopy structure of HBx in complex with DDB1, which is an essential complex for cccDNA transcription. In this structure, hydrophobic interactions within HBx were identified, and mutational analysis highlighted their importance in the HBV life cycle. Our biochemical analysis revealed that the HBx–DDB1 complex directly interacts simultaneously with NSE3, which is a component of the SMC5/6 complex, and Spindlin1. Additionally, HBx–DDB1 complex dynamics were explored via high-speed atomic force microscopy. These findings provide comprehensive insights into the structure and function of HBx in HBV replication.

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hal-05529964 , version 1 (27-02-2026)

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Hiroki Tanaka, Joao Diogo Dias, Basile Jay, Shunsuke Kita, Mina Sasaki, et al.. Structural basis of the hepatitis B virus X protein in complex with DDB1. Proceedings of the National Academy of Sciences of the United States of America, 2025, 122 (24), pp.e2421325122. ⟨10.1073/pnas.2421325122⟩. ⟨hal-05529964⟩
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