Scholarlink

<p>The HBx protein from Hepatitis B virus (HBV) is essential for replication and promotes pathogenicity during chronic infection. HBx hijacks host proteins, reprogramming them to evade antiviral defence. However, the structural basis of recruitment remains largely unknown. The HBx<sub>1-120</sub> isoform derives from integration of viral DNA into the host genome and is linked to hepatocellular carcinoma. We present an NMR-based setup to characterize HBx-host protein interactions at residue-level resolution. HBx<sub>1–120</sub> is disordered in isolation but undergoes local folding upon binding apoptosis regulator Bcl-xL and epigenetic reader Spindlin1. The HBx-Spindlin1 complex is bivalent: a hydrophobic interaction combines with a sticky patch realized via a rare inter-molecular zinc finger. HBx thus conceals the region responsible for recruiting Spindlin1 to histone tails, promoting transcription of extrachromosomal viral DNA. This mechanism exemplifies the capacity of HBx to engage diverse host factors into dynamic complexes.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

HBV HBx protein masks epigenetic reader Spindlin1 via an inter-molecular zinc finger to subvert transcriptional control

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月25日

查看全文
  • Alexis Clavier,
  • Toshinobu Shida,
  • Maxim A. Droemer,
  • Santiago Gómez-Evain,
  • Franziska von Hammerstein,
  • Julian Holzinger,
  • Mila M. Leuthold,
  • Céline Douat,
  • Anne K. Schütz

摘要

The HBx protein from Hepatitis B virus (HBV) is essential for replication and promotes pathogenicity during chronic infection. HBx hijacks host proteins, reprogramming them to evade antiviral defence. However, the structural basis of recruitment remains largely unknown. The HBx1-120 isoform derives from integration of viral DNA into the host genome and is linked to hepatocellular carcinoma. We present an NMR-based setup to characterize HBx-host protein interactions at residue-level resolution. HBx1–120 is disordered in isolation but undergoes local folding upon binding apoptosis regulator Bcl-xL and epigenetic reader Spindlin1. The HBx-Spindlin1 complex is bivalent: a hydrophobic interaction combines with a sticky patch realized via a rare inter-molecular zinc finger. HBx thus conceals the region responsible for recruiting Spindlin1 to histone tails, promoting transcription of extrachromosomal viral DNA. This mechanism exemplifies the capacity of HBx to engage diverse host factors into dynamic complexes.