Structure and nucleic acid interactions of the SΔ60 domain of the hepatitis delta virus small antigen

• 成果类型: Article
• 署名作者: Yang, Yang; Delcourte, Loic; van Belleghem, Carolanne; Fonte, Simone; Gerard, Kassandra; Baconnais, Sonia; Callon, Morgane; Le Cam, Eric; Fogeron, Marie-Laure; Levrero, Massimo; Faivre-Moskalenko, Cendrine; Bockmann, Anja; Lecoq, Lauriane
• 署名单位: Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Ecole Normale Superieure de Lyon (ENS de LYON); CHU Lyon; Universite Claude Bernard Lyon 1
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12702
• DOI: 10.1073/pnas.2411890122
• 发表日期: 2025-05-13
• 关键词: arginine-rich motifs; rna-binding-activity; protein; replication; identification; localization; residues; requires; particle; SYSTEM

摘要

Infection with hepatitis delta virus (HDV) causes the most severe form of viral hepatitis, affecting more than 15 million people worldwide. HDV is a small RNA satellite virus of the hepatitis B virus (HBV) that relies on the HBV envelope for viral particle assembly. The only specific HDV component is the ribonucleoprotein (RNP), which consists of viral RNA (vRNA) associated with the small (S) and large (L) delta antigens (HDAg). While the structure of the HDAg N-terminal assembly domain is known, here we address the structure of the remaining S degrees 60 protein using NMR. We show that S degrees 60 contains two intrinsically disordered regions separated by a helix-loop-helix motif and that this structure is conserved in the full-length protein. Solution NMR analysis revealed that S degrees 60 binds to both full-length and truncated vRNA, highlighting the role of the helical regions in submicromolar affinity interactions. The resulting complex contains approximately 120 S degrees 60 proteins per RNA. Our results provide a model for the arginine-rich domains in RNP assembly and RNA interactions. In addition, we show that a cluster of acidic residues within the structured region of S degrees 60 is critical for HDV replication, possibly mimicking the nucleosome acidic patch involved in the recruitment of chromatin remodelers. Our work thus provides the molecular basis for understanding the role of the C-terminal RNA-binding domain of S-HDAg in HDV infection.