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A novel predicted ADP-ribosyltransferase-like family conserved in eukaryotic evolution
The presence of many completely uncharacterized proteins, even in well-studied organisms such as humans, seriously hampers full understanding of the functioning of the living cells. ADP-ribosylation is a common post-translational modification of proteins; also nucleic acids and small molecules can b...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PeerJ Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955679/ https://www.ncbi.nlm.nih.gov/pubmed/33854844 http://dx.doi.org/10.7717/peerj.11051 |
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author | Wyżewski, Zbigniew Gradowski, Marcin Krysińska, Marianna Dudkiewicz, Małgorzata Pawłowski, Krzysztof |
author_facet | Wyżewski, Zbigniew Gradowski, Marcin Krysińska, Marianna Dudkiewicz, Małgorzata Pawłowski, Krzysztof |
author_sort | Wyżewski, Zbigniew |
collection | PubMed |
description | The presence of many completely uncharacterized proteins, even in well-studied organisms such as humans, seriously hampers full understanding of the functioning of the living cells. ADP-ribosylation is a common post-translational modification of proteins; also nucleic acids and small molecules can be modified by the covalent attachment of ADP-ribose. This modification, important in cellular signalling and infection processes, is usually executed by enzymes from the large superfamily of ADP-ribosyltransferases (ARTs). Here, using bioinformatics approaches, we identify a novel putative ADP-ribosyltransferase family, conserved in eukaryotic evolution, with a divergent active site. The hallmark of these proteins is the ART domain nestled between flanking leucine-rich repeat (LRR) domains. LRRs are typically involved in innate immune surveillance. The novel family appears as putative novel ADP-ribosylation-related actors, most likely pseudoenzymes. Sequence divergence and lack of clearly detectable “classical” ART active site suggests the novel domains are pseudoARTs, yet atypical ART activity, or alternative enzymatic activity cannot be excluded. We propose that this family, including its human member LRRC9, may be involved in an ancient defense mechanism, with analogies to the innate immune system, and coupling pathogen detection to ADP-ribosyltransfer or other signalling mechanisms. |
format | Online Article Text |
id | pubmed-7955679 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | PeerJ Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79556792021-04-13 A novel predicted ADP-ribosyltransferase-like family conserved in eukaryotic evolution Wyżewski, Zbigniew Gradowski, Marcin Krysińska, Marianna Dudkiewicz, Małgorzata Pawłowski, Krzysztof PeerJ Biochemistry The presence of many completely uncharacterized proteins, even in well-studied organisms such as humans, seriously hampers full understanding of the functioning of the living cells. ADP-ribosylation is a common post-translational modification of proteins; also nucleic acids and small molecules can be modified by the covalent attachment of ADP-ribose. This modification, important in cellular signalling and infection processes, is usually executed by enzymes from the large superfamily of ADP-ribosyltransferases (ARTs). Here, using bioinformatics approaches, we identify a novel putative ADP-ribosyltransferase family, conserved in eukaryotic evolution, with a divergent active site. The hallmark of these proteins is the ART domain nestled between flanking leucine-rich repeat (LRR) domains. LRRs are typically involved in innate immune surveillance. The novel family appears as putative novel ADP-ribosylation-related actors, most likely pseudoenzymes. Sequence divergence and lack of clearly detectable “classical” ART active site suggests the novel domains are pseudoARTs, yet atypical ART activity, or alternative enzymatic activity cannot be excluded. We propose that this family, including its human member LRRC9, may be involved in an ancient defense mechanism, with analogies to the innate immune system, and coupling pathogen detection to ADP-ribosyltransfer or other signalling mechanisms. PeerJ Inc. 2021-03-10 /pmc/articles/PMC7955679/ /pubmed/33854844 http://dx.doi.org/10.7717/peerj.11051 Text en ©2021 Wyżewski et al. 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 use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. |
spellingShingle | Biochemistry Wyżewski, Zbigniew Gradowski, Marcin Krysińska, Marianna Dudkiewicz, Małgorzata Pawłowski, Krzysztof A novel predicted ADP-ribosyltransferase-like family conserved in eukaryotic evolution |
title | A novel predicted ADP-ribosyltransferase-like family conserved in eukaryotic evolution |
title_full | A novel predicted ADP-ribosyltransferase-like family conserved in eukaryotic evolution |
title_fullStr | A novel predicted ADP-ribosyltransferase-like family conserved in eukaryotic evolution |
title_full_unstemmed | A novel predicted ADP-ribosyltransferase-like family conserved in eukaryotic evolution |
title_short | A novel predicted ADP-ribosyltransferase-like family conserved in eukaryotic evolution |
title_sort | novel predicted adp-ribosyltransferase-like family conserved in eukaryotic evolution |
topic | Biochemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955679/ https://www.ncbi.nlm.nih.gov/pubmed/33854844 http://dx.doi.org/10.7717/peerj.11051 |
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