Cargando…
N-Terminal Modifications of Ubiquitin via Methionine Excision, Deamination, and Arginylation Expand the Ubiquitin Code
Ubiquitin (Ub) is post-translationally modified by Ub itself or Ub-like proteins, phosphorylation, and acetylation, among others, which elicits a variety of Ub topologies and cellular functions. However, N-terminal (Nt) modifications of Ub remain unknown, except the linear head-to-tail ubiquitylatio...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society for Molecular and Cellular Biology
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8926867/ https://www.ncbi.nlm.nih.gov/pubmed/35253655 http://dx.doi.org/10.14348/molcells.2022.2027 |
_version_ | 1784670326535225344 |
---|---|
author | Nguyen, Kha The Ju, Shinyeong Kim, Sang-Yoon Lee, Chang-Seok Lee, Cheolju Hwang, Cheol-Sang |
author_facet | Nguyen, Kha The Ju, Shinyeong Kim, Sang-Yoon Lee, Chang-Seok Lee, Cheolju Hwang, Cheol-Sang |
author_sort | Nguyen, Kha The |
collection | PubMed |
description | Ubiquitin (Ub) is post-translationally modified by Ub itself or Ub-like proteins, phosphorylation, and acetylation, among others, which elicits a variety of Ub topologies and cellular functions. However, N-terminal (Nt) modifications of Ub remain unknown, except the linear head-to-tail ubiquitylation via Nt-Met. Here, using the yeast Saccharomyces cerevisiae and an Nt-arginylated Ub-specific antibody, we found that the detectable level of Ub undergoes Nt-Met excision, Nt-deamination, and Nt-arginylation. The resulting Nt-arginylated Ub and its conjugated proteins are upregulated in the stationary-growth phase or by oxidative stress. We further proved the existence of Nt-arginylated Ub in vivo and identified Nt-arginylated Ub-protein conjugates using stable isotope labeling by amino acids in cell culture (SILAC)-based tandem mass spectrometry. In silico structural modeling of Nt-arginylated Ub predicted that Nt-Arg flexibly protrudes from the surface of the Ub, thereby most likely providing a docking site for the factors that recognize it. Collectively, these results reveal unprecedented Nt-arginylated Ub and the pathway by which it is produced, which greatly expands the known complexity of the Ub code. |
format | Online Article Text |
id | pubmed-8926867 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Korean Society for Molecular and Cellular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-89268672022-03-28 N-Terminal Modifications of Ubiquitin via Methionine Excision, Deamination, and Arginylation Expand the Ubiquitin Code Nguyen, Kha The Ju, Shinyeong Kim, Sang-Yoon Lee, Chang-Seok Lee, Cheolju Hwang, Cheol-Sang Mol Cells Research Article Ubiquitin (Ub) is post-translationally modified by Ub itself or Ub-like proteins, phosphorylation, and acetylation, among others, which elicits a variety of Ub topologies and cellular functions. However, N-terminal (Nt) modifications of Ub remain unknown, except the linear head-to-tail ubiquitylation via Nt-Met. Here, using the yeast Saccharomyces cerevisiae and an Nt-arginylated Ub-specific antibody, we found that the detectable level of Ub undergoes Nt-Met excision, Nt-deamination, and Nt-arginylation. The resulting Nt-arginylated Ub and its conjugated proteins are upregulated in the stationary-growth phase or by oxidative stress. We further proved the existence of Nt-arginylated Ub in vivo and identified Nt-arginylated Ub-protein conjugates using stable isotope labeling by amino acids in cell culture (SILAC)-based tandem mass spectrometry. In silico structural modeling of Nt-arginylated Ub predicted that Nt-Arg flexibly protrudes from the surface of the Ub, thereby most likely providing a docking site for the factors that recognize it. Collectively, these results reveal unprecedented Nt-arginylated Ub and the pathway by which it is produced, which greatly expands the known complexity of the Ub code. Korean Society for Molecular and Cellular Biology 2022-03-31 2022-03-02 /pmc/articles/PMC8926867/ /pubmed/35253655 http://dx.doi.org/10.14348/molcells.2022.2027 Text en © The Korean Society for Molecular and Cellular Biology. All rights reserved. https://creativecommons.org/licenses/by-nc-sa/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ (https://creativecommons.org/licenses/by-nc-sa/3.0/) |
spellingShingle | Research Article Nguyen, Kha The Ju, Shinyeong Kim, Sang-Yoon Lee, Chang-Seok Lee, Cheolju Hwang, Cheol-Sang N-Terminal Modifications of Ubiquitin via Methionine Excision, Deamination, and Arginylation Expand the Ubiquitin Code |
title | N-Terminal Modifications of Ubiquitin via Methionine Excision, Deamination, and Arginylation Expand the Ubiquitin Code |
title_full | N-Terminal Modifications of Ubiquitin via Methionine Excision, Deamination, and Arginylation Expand the Ubiquitin Code |
title_fullStr | N-Terminal Modifications of Ubiquitin via Methionine Excision, Deamination, and Arginylation Expand the Ubiquitin Code |
title_full_unstemmed | N-Terminal Modifications of Ubiquitin via Methionine Excision, Deamination, and Arginylation Expand the Ubiquitin Code |
title_short | N-Terminal Modifications of Ubiquitin via Methionine Excision, Deamination, and Arginylation Expand the Ubiquitin Code |
title_sort | n-terminal modifications of ubiquitin via methionine excision, deamination, and arginylation expand the ubiquitin code |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8926867/ https://www.ncbi.nlm.nih.gov/pubmed/35253655 http://dx.doi.org/10.14348/molcells.2022.2027 |
work_keys_str_mv | AT nguyenkhathe nterminalmodificationsofubiquitinviamethionineexcisiondeaminationandarginylationexpandtheubiquitincode AT jushinyeong nterminalmodificationsofubiquitinviamethionineexcisiondeaminationandarginylationexpandtheubiquitincode AT kimsangyoon nterminalmodificationsofubiquitinviamethionineexcisiondeaminationandarginylationexpandtheubiquitincode AT leechangseok nterminalmodificationsofubiquitinviamethionineexcisiondeaminationandarginylationexpandtheubiquitincode AT leecheolju nterminalmodificationsofubiquitinviamethionineexcisiondeaminationandarginylationexpandtheubiquitincode AT hwangcheolsang nterminalmodificationsofubiquitinviamethionineexcisiondeaminationandarginylationexpandtheubiquitincode |