The E3 Ubiquitin Ligase TRIM21 Promotes HBV DNA Polymerase Degradation.
Amino Acid Sequence
Cell Line
DNA Replication
DNA-Directed DNA Polymerase
/ chemistry
Enzyme Stability
Hepatitis B
/ metabolism
Hepatitis B virus
/ physiology
Host-Pathogen Interactions
Humans
Models, Biological
Proteasome Endopeptidase Complex
/ metabolism
Protein Binding
Protein Interaction Domains and Motifs
Proteolysis
Ribonucleoproteins
/ metabolism
Signal Transduction
Ubiquitination
HBV DNA Pol
TRIM21
hepatitis B virus
interaction
ubiquitination
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
21 03 2020
21 03 2020
Historique:
received:
10
02
2020
revised:
18
03
2020
accepted:
19
03
2020
entrez:
5
4
2020
pubmed:
5
4
2020
medline:
18
2
2021
Statut:
epublish
Résumé
The tripartite motif (TRIM) protein family is an E3 ubiquitin ligase family. Recent reports have indicated that some TRIM proteins have antiviral functions, especially against retroviruses. However, most studies mainly focus on the relationship between TRIM21 and interferon or other antiviral effectors. The effect of TRIM21 on virus-encoded proteins remains unclear. In this study, we screened candidate interacting proteins of HBV DNA polymerase (Pol) by FLAG affinity purification and mass spectrometry assay and identified TRIM21 as its regulator. We used a coimmunoprecipitation (co-IP) assay to demonstrate that TRIM21 interacted with the TP domain of HBV DNA Pol. In addition, TRIM21 promoted the ubiquitination and degradation of HBV DNA Pol using its RING domain, which has E3 ubiquitin ligase activity. Lys260 and Lys283 of HBV DNA Pol were identified as targets for ubiquitination mediated by TRIM21. Finally, we uncovered that TRIM21 degrades HBV DNA Pol to restrict HBV DNA replication, and its SPRY domain is critical for this activity. Taken together, our results indicate that TRIM21 suppresses HBV DNA replication mainly by promoting the ubiquitination of HBV DNA Pol, which may provide a new potential target for the treatment of HBV.
Identifiants
pubmed: 32245233
pii: v12030346
doi: 10.3390/v12030346
pmc: PMC7150939
pii:
doi:
Substances chimiques
Ribonucleoproteins
0
SS-A antigen
0
DNA-Directed DNA Polymerase
EC 2.7.7.7
Proteasome Endopeptidase Complex
EC 3.4.25.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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