Structural basis of the hepatitis B virus X protein in complex with DDB1
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (15)
Hiroki Tanaka
Department of Structural Virology, National Institute of Global Health and Medicine, Japan Institute for Health Security
Joao Diogo Dias
Institut de Génétique Humaine, Laboratoire de Virologie Moléculaire, CNRS Université de Montpellier
Basile Jay
Institut de Génétique Humaine, Laboratoire de Virologie Moléculaire, CNRS Université de Montpellier
Shunsuke Kita
Laboratory of Biomolecular Science, and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, N13W8, Kitaku, Sapporo 060-8628, Japan
Mina Sasaki
Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University
Hiroyuki Takeda
Naoki Kishimoto
Shunsuke Sasaki
Department of Environmental and Molecular Health Sciences, Faculty of Life Sciences, Kumamoto University
Shogo Misumi
Masashi Mizokami
Genome Medical Sciences Project, Research Institute, National Center for Global Health and Medicine
Christine Neuveut
Institut de Génétique Humaine, Laboratoire de Virologie Moléculaire, CNRS Université de Montpellier
Takashi Sumikama
Mikihiro Shibata
Katsumi Maenaka
Shinichi Machida
Department of Structural Virology, National Institute of Global Health and Medicine, Japan Institute for Health Security