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TitleStructural basis of the hepatitis B virus X protein in complex with DDB1.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 122, Issue 24, Page e2421325122, Year 2025
Publish dateJun 17, 2025
AuthorsHiroki Tanaka / Joao Diogo Dias / Basile Jay / Shunsuke Kita / Mina Sasaki / Hiroyuki Takeda / Naoki Kishimoto / Shunsuke Sasaki / Shogo Misumi / Masashi Mizokami / Christine Neuveut / Takashi Sumikama / Mikihiro Shibata / Katsumi Maenaka / Shinichi Machida /
PubMed AbstractA 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), ...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.
External linksProc Natl Acad Sci U S A / PubMed:40512786 / PubMed Central
MethodsEM (single particle)
Resolution2.68 - 3.35 Å
Structure data

61174

9j6j

EMDB-61174, PDB-9j6j:
HBx fused DDB1 4M mutant
Method: EM (single particle) / Resolution: 2.86 Å

61175

9j6k

EMDB-61175, PDB-9j6k:
HBx complexed with DDB1
Method: EM (single particle) / Resolution: 2.68 Å

EMDB-63366: HBx R96E fused DDB1 4M mutant
Method: EM (single particle) / Resolution: 3.35 Å

Source
  • homo sapiens (human)
  • hepatitis b virus
KeywordsVIRAL PROTEIN / HBV / complex

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