HBV HBx protein masks epigenetic reader Spindlin1 via an inter-molecular zinc finger to subvert transcriptional control.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 42185260.
- Also identified by DOI 10.1038/s41467-026-72986-5 and PMC identifier 13213052.
- Licence recorded as CC BY-NC-ND.
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Abstract
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.
Medical subject headings
- Trans-Activators
- Hepatitis B virus
- Zinc Fingers
- Cell Cycle Proteins
- Microtubule-Associated Proteins
- Phosphoproteins