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. 2025 Jun 17;122(24):e2421325122.
doi: 10.1073/pnas.2421325122. Epub 2025 Jun 13.

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

Hiroki Tanaka  1 , Joao Diogo Dias  2 , Basile Jay  2 , Shunsuke Kita  3 , Mina Sasaki  3 , Hiroyuki Takeda  4 , Naoki Kishimoto  5 , Shunsuke Sasaki  5 , Shogo Misumi  5 , Masashi Mizokami  6 , Christine Neuveut  2 , Takashi Sumikama  7 , Mikihiro Shibata  7   8 , Katsumi Maenaka  3   9   10   11 , Shinichi Machida  1   12
Affiliations

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

Hiroki Tanaka et al. Proc Natl Acad Sci U S A. .

Abstract

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.

Keywords: HBx; cryo-EM structure; hepatitis B virus; high-speed AFM.

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Conflict of interest statement

Competing interests statement:The authors declare no competing interest.

References

    1. The Polaris Observatory Collaborators, Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: A modelling study. Lancet Gastroenterol. Hepatol. 3, 383–403 (2018). - PubMed
    1. Global Progress Report on HIV, Viral Hepatitis and Sexually Transmitted Infections (WorldHealth Organization, 2021).
    1. Bock C. T., Schranz P., Schröder C. H., Zentgraf H., Hepatitis B virus genome is organized into nucleosomes in the nucleus of the infected cell. Virus Genes 8, 215–229 (1994). - PubMed
    1. Bock C. T., et al. , Structural organization of the hepatitis B virus minichromosome. Mol. Biol. 307, 183–196 (2001). - PubMed
    1. Belloni L., et al. , Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function. Proc. Natl. Acad. Sci. U.S.A. 106, 19975–19979 (2009). - PMC - PubMed

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