Cargando…
Conserved degronome features governing quality control associated proteolysis
The eukaryotic proteome undergoes constant surveillance by quality control systems that either sequester, refold, or eliminate aberrant proteins by ubiquitin-dependent mechanisms. Ubiquitin-conjugation necessitates the recognition of degradation determinants, termed degrons, by their cognate E3 ubiq...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9732359/ https://www.ncbi.nlm.nih.gov/pubmed/36481666 http://dx.doi.org/10.1038/s41467-022-35298-y |
_version_ | 1784846114109784064 |
---|---|
author | Mashahreh, Bayan Armony, Shir Johansson, Kristoffer Enøe Chappleboim, Alon Friedman, Nir Gardner, Richard G. Hartmann-Petersen, Rasmus Lindorff-Larsen, Kresten Ravid, Tommer |
author_facet | Mashahreh, Bayan Armony, Shir Johansson, Kristoffer Enøe Chappleboim, Alon Friedman, Nir Gardner, Richard G. Hartmann-Petersen, Rasmus Lindorff-Larsen, Kresten Ravid, Tommer |
author_sort | Mashahreh, Bayan |
collection | PubMed |
description | The eukaryotic proteome undergoes constant surveillance by quality control systems that either sequester, refold, or eliminate aberrant proteins by ubiquitin-dependent mechanisms. Ubiquitin-conjugation necessitates the recognition of degradation determinants, termed degrons, by their cognate E3 ubiquitin-protein ligases. To learn about the distinctive properties of quality control degrons, we performed an unbiased peptidome stability screen in yeast. The search identify a large cohort of proteome-derived degrons, some of which exhibited broad E3 ligase specificity. Consequent application of a machine-learning algorithm establishes constraints governing degron potency, including the amino acid composition and secondary structure propensities. According to the set criteria, degrons with transmembrane domain-like characteristics are the most probable sequences to act as degrons. Similar quality control degrons are present in viral and human proteins, suggesting conserved degradation mechanisms. Altogether, the emerging data indicate that transmembrane domain-like degron features have been preserved in evolution as key quality control determinants of protein half-life. |
format | Online Article Text |
id | pubmed-9732359 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-97323592022-12-10 Conserved degronome features governing quality control associated proteolysis Mashahreh, Bayan Armony, Shir Johansson, Kristoffer Enøe Chappleboim, Alon Friedman, Nir Gardner, Richard G. Hartmann-Petersen, Rasmus Lindorff-Larsen, Kresten Ravid, Tommer Nat Commun Article The eukaryotic proteome undergoes constant surveillance by quality control systems that either sequester, refold, or eliminate aberrant proteins by ubiquitin-dependent mechanisms. Ubiquitin-conjugation necessitates the recognition of degradation determinants, termed degrons, by their cognate E3 ubiquitin-protein ligases. To learn about the distinctive properties of quality control degrons, we performed an unbiased peptidome stability screen in yeast. The search identify a large cohort of proteome-derived degrons, some of which exhibited broad E3 ligase specificity. Consequent application of a machine-learning algorithm establishes constraints governing degron potency, including the amino acid composition and secondary structure propensities. According to the set criteria, degrons with transmembrane domain-like characteristics are the most probable sequences to act as degrons. Similar quality control degrons are present in viral and human proteins, suggesting conserved degradation mechanisms. Altogether, the emerging data indicate that transmembrane domain-like degron features have been preserved in evolution as key quality control determinants of protein half-life. Nature Publishing Group UK 2022-12-08 /pmc/articles/PMC9732359/ /pubmed/36481666 http://dx.doi.org/10.1038/s41467-022-35298-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Mashahreh, Bayan Armony, Shir Johansson, Kristoffer Enøe Chappleboim, Alon Friedman, Nir Gardner, Richard G. Hartmann-Petersen, Rasmus Lindorff-Larsen, Kresten Ravid, Tommer Conserved degronome features governing quality control associated proteolysis |
title | Conserved degronome features governing quality control associated proteolysis |
title_full | Conserved degronome features governing quality control associated proteolysis |
title_fullStr | Conserved degronome features governing quality control associated proteolysis |
title_full_unstemmed | Conserved degronome features governing quality control associated proteolysis |
title_short | Conserved degronome features governing quality control associated proteolysis |
title_sort | conserved degronome features governing quality control associated proteolysis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9732359/ https://www.ncbi.nlm.nih.gov/pubmed/36481666 http://dx.doi.org/10.1038/s41467-022-35298-y |
work_keys_str_mv | AT mashahrehbayan conserveddegronomefeaturesgoverningqualitycontrolassociatedproteolysis AT armonyshir conserveddegronomefeaturesgoverningqualitycontrolassociatedproteolysis AT johanssonkristofferenøe conserveddegronomefeaturesgoverningqualitycontrolassociatedproteolysis AT chappleboimalon conserveddegronomefeaturesgoverningqualitycontrolassociatedproteolysis AT friedmannir conserveddegronomefeaturesgoverningqualitycontrolassociatedproteolysis AT gardnerrichardg conserveddegronomefeaturesgoverningqualitycontrolassociatedproteolysis AT hartmannpetersenrasmus conserveddegronomefeaturesgoverningqualitycontrolassociatedproteolysis AT lindorfflarsenkresten conserveddegronomefeaturesgoverningqualitycontrolassociatedproteolysis AT ravidtommer conserveddegronomefeaturesgoverningqualitycontrolassociatedproteolysis |