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Updated protein domain annotation of the PARP protein family sheds new light on biological function
AlphaFold2 and related computational tools have greatly aided studies of structural biology through their ability to accurately predict protein structures. In the present work, we explored AF2 structural models of the 17 canonical members of the human PARP protein family and supplemented this analys...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10450202/ https://www.ncbi.nlm.nih.gov/pubmed/37326024 http://dx.doi.org/10.1093/nar/gkad514 |
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author | Suskiewicz, Marcin J Munnur, Deeksha Strømland, Øyvind Yang, Ji-Chun Easton, Laura E Chatrin, Chatrin Zhu, Kang Baretić, Domagoj Goffinont, Stéphane Schuller, Marion Wu, Wing-Fung Elkins, Jonathan M Ahel, Dragana Sanyal, Sumana Neuhaus, David Ahel, Ivan |
author_facet | Suskiewicz, Marcin J Munnur, Deeksha Strømland, Øyvind Yang, Ji-Chun Easton, Laura E Chatrin, Chatrin Zhu, Kang Baretić, Domagoj Goffinont, Stéphane Schuller, Marion Wu, Wing-Fung Elkins, Jonathan M Ahel, Dragana Sanyal, Sumana Neuhaus, David Ahel, Ivan |
author_sort | Suskiewicz, Marcin J |
collection | PubMed |
description | AlphaFold2 and related computational tools have greatly aided studies of structural biology through their ability to accurately predict protein structures. In the present work, we explored AF2 structural models of the 17 canonical members of the human PARP protein family and supplemented this analysis with new experiments and an overview of recent published data. PARP proteins are typically involved in the modification of proteins and nucleic acids through mono or poly(ADP-ribosyl)ation, but this function can be modulated by the presence of various auxiliary protein domains. Our analysis provides a comprehensive view of the structured domains and long intrinsically disordered regions within human PARPs, offering a revised basis for understanding the function of these proteins. Among other functional insights, the study provides a model of PARP1 domain dynamics in the DNA-free and DNA-bound states and enhances the connection between ADP-ribosylation and RNA biology and between ADP-ribosylation and ubiquitin-like modifications by predicting putative RNA-binding domains and E2-related RWD domains in certain PARPs. In line with the bioinformatic analysis, we demonstrate for the first time PARP14’s RNA-binding capability and RNA ADP-ribosylation activity in vitro. While our insights align with existing experimental data and are probably accurate, they need further validation through experiments. |
format | Online Article Text |
id | pubmed-10450202 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-104502022023-08-26 Updated protein domain annotation of the PARP protein family sheds new light on biological function Suskiewicz, Marcin J Munnur, Deeksha Strømland, Øyvind Yang, Ji-Chun Easton, Laura E Chatrin, Chatrin Zhu, Kang Baretić, Domagoj Goffinont, Stéphane Schuller, Marion Wu, Wing-Fung Elkins, Jonathan M Ahel, Dragana Sanyal, Sumana Neuhaus, David Ahel, Ivan Nucleic Acids Res Structural Biology AlphaFold2 and related computational tools have greatly aided studies of structural biology through their ability to accurately predict protein structures. In the present work, we explored AF2 structural models of the 17 canonical members of the human PARP protein family and supplemented this analysis with new experiments and an overview of recent published data. PARP proteins are typically involved in the modification of proteins and nucleic acids through mono or poly(ADP-ribosyl)ation, but this function can be modulated by the presence of various auxiliary protein domains. Our analysis provides a comprehensive view of the structured domains and long intrinsically disordered regions within human PARPs, offering a revised basis for understanding the function of these proteins. Among other functional insights, the study provides a model of PARP1 domain dynamics in the DNA-free and DNA-bound states and enhances the connection between ADP-ribosylation and RNA biology and between ADP-ribosylation and ubiquitin-like modifications by predicting putative RNA-binding domains and E2-related RWD domains in certain PARPs. In line with the bioinformatic analysis, we demonstrate for the first time PARP14’s RNA-binding capability and RNA ADP-ribosylation activity in vitro. While our insights align with existing experimental data and are probably accurate, they need further validation through experiments. Oxford University Press 2023-06-16 /pmc/articles/PMC10450202/ /pubmed/37326024 http://dx.doi.org/10.1093/nar/gkad514 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Structural Biology Suskiewicz, Marcin J Munnur, Deeksha Strømland, Øyvind Yang, Ji-Chun Easton, Laura E Chatrin, Chatrin Zhu, Kang Baretić, Domagoj Goffinont, Stéphane Schuller, Marion Wu, Wing-Fung Elkins, Jonathan M Ahel, Dragana Sanyal, Sumana Neuhaus, David Ahel, Ivan Updated protein domain annotation of the PARP protein family sheds new light on biological function |
title | Updated protein domain annotation of the PARP protein family sheds new light on biological function |
title_full | Updated protein domain annotation of the PARP protein family sheds new light on biological function |
title_fullStr | Updated protein domain annotation of the PARP protein family sheds new light on biological function |
title_full_unstemmed | Updated protein domain annotation of the PARP protein family sheds new light on biological function |
title_short | Updated protein domain annotation of the PARP protein family sheds new light on biological function |
title_sort | updated protein domain annotation of the parp protein family sheds new light on biological function |
topic | Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10450202/ https://www.ncbi.nlm.nih.gov/pubmed/37326024 http://dx.doi.org/10.1093/nar/gkad514 |
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