Viral macro domains reverse protein ADP-ribosylation.
ADP-ribosylation is a posttranslational protein modification in which ADP-ribose is transferred from NAD+ to specific acceptors to regulate a wide variety of cellular processes. The macro domain is an ancient and highly evolutionarily conserved protein domain widely distributed throughout all kingdo...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Society for Microbiology
2016
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| _version_ | 1826289930064625664 |
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| author | Li, C Debing, Y Jankevicius, G Neyts, J Ahel, I Coutard, B Canard, B |
| author_facet | Li, C Debing, Y Jankevicius, G Neyts, J Ahel, I Coutard, B Canard, B |
| author_sort | Li, C |
| collection | OXFORD |
| description | ADP-ribosylation is a posttranslational protein modification in which ADP-ribose is transferred from NAD+ to specific acceptors to regulate a wide variety of cellular processes. The macro domain is an ancient and highly evolutionarily conserved protein domain widely distributed throughout all kingdoms of life, including viruses. The human TARG1/C6orf130, MacroD1, and MacroD2 proteins can reverse ADP-ribosylation by acting on ADP-ribosylated substrates through the hydrolytic activity of their macro domains. Here, we report that the macro domain from hepatitis E virus (HEV) serves as an ADP-ribose-protein hydrolase for mono-ADP-ribose (MAR) and poly(ADP-ribose) (PAR) chain removal (de-MARylation and de-PARylation, respectively) from mono- and poly(ADP)-ribosylated proteins, respectively. The presence of the HEV helicase incisdramatically increases the binding of the macro domain to poly(ADP-ribose) and stimulates the de-PARylation activity. Abrogation of the latter dramatically decreases replication of an HEV subgenomic replicon. The de-MARylation activity is present in all three pathogenic positive-sense, single-stranded RNA [(+)ssRNA] virus families which carry a macro domain:Coronaviridae(severe acute respiratory syndrome coronavirus and human coronavirus 229E),Togaviridae(Venezuelan equine encephalitis virus), andHepeviridae (HEV), indicating that it might be a significant tropism and/or pathogenic determinant. |
| first_indexed | 2024-03-07T02:36:25Z |
| format | Journal article |
| id | oxford-uuid:a8f05972-f2d5-4d20-bfef-e74050a5eb30 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:36:25Z |
| publishDate | 2016 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | oxford-uuid:a8f05972-f2d5-4d20-bfef-e74050a5eb302022-03-27T03:05:04ZViral macro domains reverse protein ADP-ribosylation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a8f05972-f2d5-4d20-bfef-e74050a5eb30EnglishSymplectic Elements at OxfordAmerican Society for Microbiology2016Li, CDebing, YJankevicius, GNeyts, JAhel, ICoutard, BCanard, BADP-ribosylation is a posttranslational protein modification in which ADP-ribose is transferred from NAD+ to specific acceptors to regulate a wide variety of cellular processes. The macro domain is an ancient and highly evolutionarily conserved protein domain widely distributed throughout all kingdoms of life, including viruses. The human TARG1/C6orf130, MacroD1, and MacroD2 proteins can reverse ADP-ribosylation by acting on ADP-ribosylated substrates through the hydrolytic activity of their macro domains. Here, we report that the macro domain from hepatitis E virus (HEV) serves as an ADP-ribose-protein hydrolase for mono-ADP-ribose (MAR) and poly(ADP-ribose) (PAR) chain removal (de-MARylation and de-PARylation, respectively) from mono- and poly(ADP)-ribosylated proteins, respectively. The presence of the HEV helicase incisdramatically increases the binding of the macro domain to poly(ADP-ribose) and stimulates the de-PARylation activity. Abrogation of the latter dramatically decreases replication of an HEV subgenomic replicon. The de-MARylation activity is present in all three pathogenic positive-sense, single-stranded RNA [(+)ssRNA] virus families which carry a macro domain:Coronaviridae(severe acute respiratory syndrome coronavirus and human coronavirus 229E),Togaviridae(Venezuelan equine encephalitis virus), andHepeviridae (HEV), indicating that it might be a significant tropism and/or pathogenic determinant. |
| spellingShingle | Li, C Debing, Y Jankevicius, G Neyts, J Ahel, I Coutard, B Canard, B Viral macro domains reverse protein ADP-ribosylation. |
| title | Viral macro domains reverse protein ADP-ribosylation. |
| title_full | Viral macro domains reverse protein ADP-ribosylation. |
| title_fullStr | Viral macro domains reverse protein ADP-ribosylation. |
| title_full_unstemmed | Viral macro domains reverse protein ADP-ribosylation. |
| title_short | Viral macro domains reverse protein ADP-ribosylation. |
| title_sort | viral macro domains reverse protein adp ribosylation |
| work_keys_str_mv | AT lic viralmacrodomainsreverseproteinadpribosylation AT debingy viralmacrodomainsreverseproteinadpribosylation AT jankeviciusg viralmacrodomainsreverseproteinadpribosylation AT neytsj viralmacrodomainsreverseproteinadpribosylation AT aheli viralmacrodomainsreverseproteinadpribosylation AT coutardb viralmacrodomainsreverseproteinadpribosylation AT canardb viralmacrodomainsreverseproteinadpribosylation |