Related Experiment Video
Updated: Mar 17, 2026
12:43
Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE
Published on: July 29, 2014
12.7K
Viral Macro Domains Reverse Protein ADP-Ribosylation
Changqing Li1, Yannick Debing2, Gytis Jankevicius3
1CNRS, AFMB UMR 7257, Marseille, France Aix-Marseille Université, AFMB UMR 7257, Marseille, France.
Journal of Virology
|July 22, 2016
Summary
Hepatitis E virus (HEV) macro domain removes ADP-ribosylation marks from proteins, a process crucial for viral replication. This de-ADP-ribosylation activity is conserved in pathogenic (+)ssRNA viruses and may influence viral tropism and pathogenicity.
Area of Science:
- Molecular Biology
- Virology
- Biochemistry
Background:
- ADP-ribosylation is a critical posttranslational modification regulating diverse cellular functions.
- Macro domains are conserved protein modules found across life, including in viruses, involved in ADP-ribosylation.
- Human proteins like TARG1, MacroD1, and MacroD2 hydrolyze ADP-ribosylated substrates.
Purpose of the Study:
- To investigate the enzymatic activity of the hepatitis E virus (HEV) macro domain.
- To determine the role of the HEV macro domain and adjacent helicase in viral replication.
- To assess the prevalence and potential significance of viral macro domain de-ADP-ribosylation activity in pathogenic viruses.
Main Methods:
- Biochemical assays to characterize the de-ADP-ribosylation activity (de-MARylation and de-PARylation) of the HEV macro domain.
- In vitro binding assays to assess the interaction between the HEV macro domain and poly(ADP-ribose) (PAR).
- Functional assays using HEV subgenomic replicons to evaluate the impact of macro domain activity on viral replication.
Main Results:
- The HEV macro domain functions as an ADP-ribose-protein hydrolase, removing both mono-ADP-ribose (MAR) and poly(ADP-ribose) (PAR) chains.
- The adjacent HEV helicase domain significantly enhances PAR binding and de-PARylation activity.
- Inhibition of de-PARylation activity markedly reduces HEV subgenomic replicon replication.
- De-MARylation activity is conserved in Coronaviridae, Togaviridae, and Hepeviridae, suggesting a role in viral tropism and pathogenicity.
Conclusions:
- The HEV macro domain's hydrolytic activity is essential for efficient viral replication.
- The viral macro domain's ability to reverse cellular ADP-ribosylation may be a key viral strategy.
- Conserved de-ADP-ribosylation activity across pathogenic (+)ssRNA viruses highlights its potential as a significant determinant of viral tropism and pathogenicity.
Related Concept Videos
02:28Leaky Scanning
5.8K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.8K
01:10Retrovirus Life Cycles
50.3K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
50.3K
01:29Viruses with RNA Genomes
1.2K
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
1.2K
01:34Directing Proteins to the Rough Endoplasmic Reticulum
18.2K
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
18.2K
01:14Rab Proteins
5.4K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
5.4K
01:26Size and Structure of Viral Genomes
999
Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
999