Abstract
• The expression level of TRIM21 in patients is negatively correlated with the replication and integration of HBV. • TRIM21 was found to trigger non-proteolytic ubiquitination of X protein of HBV. • This study proposes that the PRYSPRY and RING domains in TRIM21 dimer can form a docking conformation for HBx binding. • TRIM21-mediated HBx ubiquitination disrupts the DDB1 recruitment to HBx and stabilize Smc6.