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Dynamics-Based Regulatory Switches of Type II Antitoxins: Insights into New Antimicrobial Discovery
Type II toxin-antitoxin (TA) modules are prevalent in prokaryotes and are involved in cell maintenance and survival under harsh environmental conditions, including nutrient deficiency, antibiotic treatment, and human immune responses. Typically, the type II TA system consists of two protein componen...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135005/ https://www.ncbi.nlm.nih.gov/pubmed/37106997 http://dx.doi.org/10.3390/antibiotics12040637 |
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author | Lee, Ki-Young Lee, Bong-Jin |
author_facet | Lee, Ki-Young Lee, Bong-Jin |
author_sort | Lee, Ki-Young |
collection | PubMed |
description | Type II toxin-antitoxin (TA) modules are prevalent in prokaryotes and are involved in cell maintenance and survival under harsh environmental conditions, including nutrient deficiency, antibiotic treatment, and human immune responses. Typically, the type II TA system consists of two protein components: a toxin that inhibits an essential cellular process and an antitoxin that neutralizes its toxicity. Antitoxins of type II TA modules typically contain the structured DNA-binding domain responsible for TA transcription repression and an intrinsically disordered region (IDR) at the C-terminus that directly binds to and neutralizes the toxin. Recently accumulated data have suggested that the antitoxin’s IDRs exhibit variable degrees of preexisting helical conformations that stabilize upon binding to the corresponding toxin or operator DNA and function as a central hub in regulatory protein interaction networks of the type II TA system. However, the biological and pathogenic functions of the antitoxin’s IDRs have not been well discussed compared with those of IDRs from the eukaryotic proteome. Here, we focus on the current state of knowledge about the versatile roles of IDRs of type II antitoxins in TA regulation and provide insights into the discovery of new antibiotic candidates that induce toxin activation/reactivation and cell death by modulating the regulatory dynamics or allostery of the antitoxin. |
format | Online Article Text |
id | pubmed-10135005 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101350052023-04-28 Dynamics-Based Regulatory Switches of Type II Antitoxins: Insights into New Antimicrobial Discovery Lee, Ki-Young Lee, Bong-Jin Antibiotics (Basel) Perspective Type II toxin-antitoxin (TA) modules are prevalent in prokaryotes and are involved in cell maintenance and survival under harsh environmental conditions, including nutrient deficiency, antibiotic treatment, and human immune responses. Typically, the type II TA system consists of two protein components: a toxin that inhibits an essential cellular process and an antitoxin that neutralizes its toxicity. Antitoxins of type II TA modules typically contain the structured DNA-binding domain responsible for TA transcription repression and an intrinsically disordered region (IDR) at the C-terminus that directly binds to and neutralizes the toxin. Recently accumulated data have suggested that the antitoxin’s IDRs exhibit variable degrees of preexisting helical conformations that stabilize upon binding to the corresponding toxin or operator DNA and function as a central hub in regulatory protein interaction networks of the type II TA system. However, the biological and pathogenic functions of the antitoxin’s IDRs have not been well discussed compared with those of IDRs from the eukaryotic proteome. Here, we focus on the current state of knowledge about the versatile roles of IDRs of type II antitoxins in TA regulation and provide insights into the discovery of new antibiotic candidates that induce toxin activation/reactivation and cell death by modulating the regulatory dynamics or allostery of the antitoxin. MDPI 2023-03-23 /pmc/articles/PMC10135005/ /pubmed/37106997 http://dx.doi.org/10.3390/antibiotics12040637 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Perspective Lee, Ki-Young Lee, Bong-Jin Dynamics-Based Regulatory Switches of Type II Antitoxins: Insights into New Antimicrobial Discovery |
title | Dynamics-Based Regulatory Switches of Type II Antitoxins: Insights into New Antimicrobial Discovery |
title_full | Dynamics-Based Regulatory Switches of Type II Antitoxins: Insights into New Antimicrobial Discovery |
title_fullStr | Dynamics-Based Regulatory Switches of Type II Antitoxins: Insights into New Antimicrobial Discovery |
title_full_unstemmed | Dynamics-Based Regulatory Switches of Type II Antitoxins: Insights into New Antimicrobial Discovery |
title_short | Dynamics-Based Regulatory Switches of Type II Antitoxins: Insights into New Antimicrobial Discovery |
title_sort | dynamics-based regulatory switches of type ii antitoxins: insights into new antimicrobial discovery |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135005/ https://www.ncbi.nlm.nih.gov/pubmed/37106997 http://dx.doi.org/10.3390/antibiotics12040637 |
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