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The Structure and Immune Regulatory Implications of the Ubiquitin-Like Tandem Domain Within an Avian 2’-5’ Oligoadenylate Synthetase-Like Protein

Post-translational modification of host and viral proteins by ubiquitin and ubiquitin-like proteins plays a key role in a host’s ability to mount an effective immune response. Avian species lack a ubiquitin-like protein found in mammals and other non-avian reptiles; interferon stimulated gene produc...

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Autores principales: Shepard, Justin D., Freitas, Brendan T., Rodriguez, Sergio E., Scholte, Florine E. M., Baker, Kailee, Hutchison, Madelyn R., Longo, Jaron E., Miller, Holden C., O’Boyle, Brady M., Tandon, Aarushi, Zhao, Peng, Grimsey, Neil J., Wells, Lance, Bergeron, Éric, Pegan, Scott D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764230/
https://www.ncbi.nlm.nih.gov/pubmed/35058932
http://dx.doi.org/10.3389/fimmu.2021.794664
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author Shepard, Justin D.
Freitas, Brendan T.
Rodriguez, Sergio E.
Scholte, Florine E. M.
Baker, Kailee
Hutchison, Madelyn R.
Longo, Jaron E.
Miller, Holden C.
O’Boyle, Brady M.
Tandon, Aarushi
Zhao, Peng
Grimsey, Neil J.
Wells, Lance
Bergeron, Éric
Pegan, Scott D.
author_facet Shepard, Justin D.
Freitas, Brendan T.
Rodriguez, Sergio E.
Scholte, Florine E. M.
Baker, Kailee
Hutchison, Madelyn R.
Longo, Jaron E.
Miller, Holden C.
O’Boyle, Brady M.
Tandon, Aarushi
Zhao, Peng
Grimsey, Neil J.
Wells, Lance
Bergeron, Éric
Pegan, Scott D.
author_sort Shepard, Justin D.
collection PubMed
description Post-translational modification of host and viral proteins by ubiquitin and ubiquitin-like proteins plays a key role in a host’s ability to mount an effective immune response. Avian species lack a ubiquitin-like protein found in mammals and other non-avian reptiles; interferon stimulated gene product 15 (ISG15). ISG15 serves as a messenger molecule and can be conjugated to both host and viral proteins leading them to be stabilized, degraded, or sequestered. Structurally, ISG15 is comprised of a tandem ubiquitin-like domain (Ubl), which serves as the motif for post-translational modification. The 2’-5’ oligoadenylate synthetase-like proteins (OASL) also encode two Ubl domains in series near its C-terminus which binds OASL to retinoic acid inducible gene-I (RIG-I). This protein-protein interaction increases the sensitivity of RIG-I and results in an enhanced production of type 1 interferons and a robust immune response. Unlike human and other mammalian OASL homologues, avian OASLs terminate their tandem Ubl domains with the same LRLRGG motif found in ubiquitin and ISG15, a motif required for their conjugation to proteins. Chickens, however, lack RIG-I, raising the question of structural and functional characteristics of chicken OASL (chOASL). By investigating chOASL, the evolutionary history of viruses with deubiquitinases can be explored and drivers of species specificity for these viruses may be uncovered. Here we show that the chOASL tandem Ubl domains shares structural characteristics with mammalian ISG15, and that chOASL can oligomerize and conjugate to itself. In addition, the ISG15-like features of avian OASLs and how they impact interactions with viral deubiquitinases and deISGylases are explored.
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spelling pubmed-87642302022-01-19 The Structure and Immune Regulatory Implications of the Ubiquitin-Like Tandem Domain Within an Avian 2’-5’ Oligoadenylate Synthetase-Like Protein Shepard, Justin D. Freitas, Brendan T. Rodriguez, Sergio E. Scholte, Florine E. M. Baker, Kailee Hutchison, Madelyn R. Longo, Jaron E. Miller, Holden C. O’Boyle, Brady M. Tandon, Aarushi Zhao, Peng Grimsey, Neil J. Wells, Lance Bergeron, Éric Pegan, Scott D. Front Immunol Immunology Post-translational modification of host and viral proteins by ubiquitin and ubiquitin-like proteins plays a key role in a host’s ability to mount an effective immune response. Avian species lack a ubiquitin-like protein found in mammals and other non-avian reptiles; interferon stimulated gene product 15 (ISG15). ISG15 serves as a messenger molecule and can be conjugated to both host and viral proteins leading them to be stabilized, degraded, or sequestered. Structurally, ISG15 is comprised of a tandem ubiquitin-like domain (Ubl), which serves as the motif for post-translational modification. The 2’-5’ oligoadenylate synthetase-like proteins (OASL) also encode two Ubl domains in series near its C-terminus which binds OASL to retinoic acid inducible gene-I (RIG-I). This protein-protein interaction increases the sensitivity of RIG-I and results in an enhanced production of type 1 interferons and a robust immune response. Unlike human and other mammalian OASL homologues, avian OASLs terminate their tandem Ubl domains with the same LRLRGG motif found in ubiquitin and ISG15, a motif required for their conjugation to proteins. Chickens, however, lack RIG-I, raising the question of structural and functional characteristics of chicken OASL (chOASL). By investigating chOASL, the evolutionary history of viruses with deubiquitinases can be explored and drivers of species specificity for these viruses may be uncovered. Here we show that the chOASL tandem Ubl domains shares structural characteristics with mammalian ISG15, and that chOASL can oligomerize and conjugate to itself. In addition, the ISG15-like features of avian OASLs and how they impact interactions with viral deubiquitinases and deISGylases are explored. Frontiers Media S.A. 2022-01-04 /pmc/articles/PMC8764230/ /pubmed/35058932 http://dx.doi.org/10.3389/fimmu.2021.794664 Text en Copyright © 2022 Shepard, Freitas, Rodriguez, Scholte, Baker, Hutchison, Longo, Miller, O’Boyle, Tandon, Zhao, Grimsey, Wells, Bergeron and Pegan https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Shepard, Justin D.
Freitas, Brendan T.
Rodriguez, Sergio E.
Scholte, Florine E. M.
Baker, Kailee
Hutchison, Madelyn R.
Longo, Jaron E.
Miller, Holden C.
O’Boyle, Brady M.
Tandon, Aarushi
Zhao, Peng
Grimsey, Neil J.
Wells, Lance
Bergeron, Éric
Pegan, Scott D.
The Structure and Immune Regulatory Implications of the Ubiquitin-Like Tandem Domain Within an Avian 2’-5’ Oligoadenylate Synthetase-Like Protein
title The Structure and Immune Regulatory Implications of the Ubiquitin-Like Tandem Domain Within an Avian 2’-5’ Oligoadenylate Synthetase-Like Protein
title_full The Structure and Immune Regulatory Implications of the Ubiquitin-Like Tandem Domain Within an Avian 2’-5’ Oligoadenylate Synthetase-Like Protein
title_fullStr The Structure and Immune Regulatory Implications of the Ubiquitin-Like Tandem Domain Within an Avian 2’-5’ Oligoadenylate Synthetase-Like Protein
title_full_unstemmed The Structure and Immune Regulatory Implications of the Ubiquitin-Like Tandem Domain Within an Avian 2’-5’ Oligoadenylate Synthetase-Like Protein
title_short The Structure and Immune Regulatory Implications of the Ubiquitin-Like Tandem Domain Within an Avian 2’-5’ Oligoadenylate Synthetase-Like Protein
title_sort structure and immune regulatory implications of the ubiquitin-like tandem domain within an avian 2’-5’ oligoadenylate synthetase-like protein
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764230/
https://www.ncbi.nlm.nih.gov/pubmed/35058932
http://dx.doi.org/10.3389/fimmu.2021.794664
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