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Characterization of an Aedes ADP-Ribosylation Protein Domain and Role of Post-Translational Modification during Chikungunya Virus Infection
Poly ADP-ribose polymerases (PARPs) catalyze ADP-ribosylation, a subclass of post-translational modification (PTM). Mono-ADP-ribose (MAR) moieties bind to target molecules such as proteins and nucleic acids, and are added as part of the process which also leads to formation of polymer chains of ADP-...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10223269/ https://www.ncbi.nlm.nih.gov/pubmed/37242388 http://dx.doi.org/10.3390/pathogens12050718 |
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author | Kumar, Ramesh Mehta, Divya Nayak, Debasis Sunil, Sujatha |
author_facet | Kumar, Ramesh Mehta, Divya Nayak, Debasis Sunil, Sujatha |
author_sort | Kumar, Ramesh |
collection | PubMed |
description | Poly ADP-ribose polymerases (PARPs) catalyze ADP-ribosylation, a subclass of post-translational modification (PTM). Mono-ADP-ribose (MAR) moieties bind to target molecules such as proteins and nucleic acids, and are added as part of the process which also leads to formation of polymer chains of ADP-ribose. ADP-ribosylation is reversible; its removal is carried out by ribosyl hydrolases such as PARG (poly ADP-ribose glycohydrolase), TARG (terminal ADP-ribose protein glycohydrolase), macrodomain, etc. In this study, the catalytic domain of Aedes aegypti tankyrase was expressed in bacteria and purified. The tankyrase PARP catalytic domain was found to be enzymatically active, as demonstrated by an in vitro poly ADP-ribosylation (PARylation) experiment. Using in vitro ADP-ribosylation assay, we further demonstrate that the chikungunya virus (CHIKV) nsp3 (non-structural protein 3) macrodomain inhibits ADP-ribosylation in a time-dependent way. We have also demonstrated that transfection of the CHIKV nsP3 macrodomain increases the CHIKV viral titer in mosquito cells, suggesting that ADP-ribosylation may play a significant role in viral replication. |
format | Online Article Text |
id | pubmed-10223269 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102232692023-05-28 Characterization of an Aedes ADP-Ribosylation Protein Domain and Role of Post-Translational Modification during Chikungunya Virus Infection Kumar, Ramesh Mehta, Divya Nayak, Debasis Sunil, Sujatha Pathogens Article Poly ADP-ribose polymerases (PARPs) catalyze ADP-ribosylation, a subclass of post-translational modification (PTM). Mono-ADP-ribose (MAR) moieties bind to target molecules such as proteins and nucleic acids, and are added as part of the process which also leads to formation of polymer chains of ADP-ribose. ADP-ribosylation is reversible; its removal is carried out by ribosyl hydrolases such as PARG (poly ADP-ribose glycohydrolase), TARG (terminal ADP-ribose protein glycohydrolase), macrodomain, etc. In this study, the catalytic domain of Aedes aegypti tankyrase was expressed in bacteria and purified. The tankyrase PARP catalytic domain was found to be enzymatically active, as demonstrated by an in vitro poly ADP-ribosylation (PARylation) experiment. Using in vitro ADP-ribosylation assay, we further demonstrate that the chikungunya virus (CHIKV) nsp3 (non-structural protein 3) macrodomain inhibits ADP-ribosylation in a time-dependent way. We have also demonstrated that transfection of the CHIKV nsP3 macrodomain increases the CHIKV viral titer in mosquito cells, suggesting that ADP-ribosylation may play a significant role in viral replication. MDPI 2023-05-16 /pmc/articles/PMC10223269/ /pubmed/37242388 http://dx.doi.org/10.3390/pathogens12050718 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kumar, Ramesh Mehta, Divya Nayak, Debasis Sunil, Sujatha Characterization of an Aedes ADP-Ribosylation Protein Domain and Role of Post-Translational Modification during Chikungunya Virus Infection |
title | Characterization of an Aedes ADP-Ribosylation Protein Domain and Role of Post-Translational Modification during Chikungunya Virus Infection |
title_full | Characterization of an Aedes ADP-Ribosylation Protein Domain and Role of Post-Translational Modification during Chikungunya Virus Infection |
title_fullStr | Characterization of an Aedes ADP-Ribosylation Protein Domain and Role of Post-Translational Modification during Chikungunya Virus Infection |
title_full_unstemmed | Characterization of an Aedes ADP-Ribosylation Protein Domain and Role of Post-Translational Modification during Chikungunya Virus Infection |
title_short | Characterization of an Aedes ADP-Ribosylation Protein Domain and Role of Post-Translational Modification during Chikungunya Virus Infection |
title_sort | characterization of an aedes adp-ribosylation protein domain and role of post-translational modification during chikungunya virus infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10223269/ https://www.ncbi.nlm.nih.gov/pubmed/37242388 http://dx.doi.org/10.3390/pathogens12050718 |
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