Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Ki-Young, Lee, Bong-Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785031872965771264
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
work_keys_str_mv AT leekiyoung dynamicsbasedregulatoryswitchesoftypeiiantitoxinsinsightsintonewantimicrobialdiscovery
AT leebongjin dynamicsbasedregulatoryswitchesoftypeiiantitoxinsinsightsintonewantimicrobialdiscovery