Strain-Dependent Recognition of a Unique Degradation Motif by ClpXP in <named-content content-type="genus-species">Streptococcus mutans</named-content>

ABSTRACT Streptococcus mutans, a dental pathogen, has a remarkable ability to cope with environmental stresses. Under stress conditions, cytoplasmic proteases play a major role in controlling the stability of regulatory proteins and preventing accumulation of damaged and misfolded proteins. ClpXP, a...

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Autores principales:	Biswanath Jana, Liang Tao, Indranil Biswas
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	ClpXP motif Streptococcus mutans adaptor proteins regulated proteolysis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d92f84afab98425a834348f1c016d73e
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spelling	oai:doaj.org-article:d92f84afab98425a834348f1c016d73e2021-11-15T15:22:04ZStrain-Dependent Recognition of a Unique Degradation Motif by ClpXP in <named-content content-type="genus-species">Streptococcus mutans</named-content>10.1128/mSphere.00287-162379-5042https://doaj.org/article/d92f84afab98425a834348f1c016d73e2016-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00287-16https://doaj.org/toc/2379-5042ABSTRACT Streptococcus mutans, a dental pathogen, has a remarkable ability to cope with environmental stresses. Under stress conditions, cytoplasmic proteases play a major role in controlling the stability of regulatory proteins and preventing accumulation of damaged and misfolded proteins. ClpXP, a well-conserved cytoplasmic proteolytic system, is crucial in maintaining cellular homeostasis in bacteria. ClpX is primarily responsible for recognition of substrates and subsequent translocation of unfolded substrates into the ClpP proteolytic compartment for degradation. In Escherichia coli, ClpX recognizes distinct motifs present at the C-terminal end of target proteins. However, recognition sequences for ClpXP in other bacteria, including S. mutans, are not known. In this study, using two-dimensional (2D) polyacrylamide gel electrophoresis (PAGE) analysis, we have identified several putative substrates for S. mutans ClpXP. SsbA, which encodes a small DNA binding protein, is one such substrate that is degraded by ClpXP. By sequential deletions, we found that the last 3 C-terminal amino acids, LPF, are sufficient for ClpXP-mediated degradation. Addition of LPF at the C-terminal end of green fluorescent protein (GFP) rendered the protein completely degradable by ClpXP. Alterations of this tripeptide motif impeded ClpXP-mediated degradation. However, recognition of LPF by ClpXP is highly specific to some S. mutans strains (UA159, UA130, and N3209) since not all S. mutans strains recognize the motif. We speculate that an adaptor protein is involved in either substrate recognition or substrate degradation by ClpXP. Nevertheless, this is the first report of a unique recognition sequence for ClpXP in streptococci. IMPORTANCE Regulated proteolysis in bacteria is an important biological process that maintains protein homeostasis. ClpXP, an intracellular proteolytic complex, is the primary protease that is responsible for protein turnover. While the substrates for ClpXP were identified in Escherichia coli, the substrates for vast majority of bacteria are currently unknown. In this study, we identified a unique substrate for ClpXP-mediated degradation in Streptococcus mutans, a dental pathogen. We also found that a small motif composed of 3 amino acids is sufficient for ClpXP-mediated degradation. Identification of this motif will clearly help us to understand the pathogenesis of this organism and other related pathogens.Biswanath JanaLiang TaoIndranil BiswasAmerican Society for MicrobiologyarticleClpXPmotifStreptococcus mutansadaptor proteinsregulated proteolysisMicrobiologyQR1-502ENmSphere, Vol 1, Iss 6 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	ClpXP motif Streptococcus mutans adaptor proteins regulated proteolysis Microbiology QR1-502
spellingShingle	ClpXP motif Streptococcus mutans adaptor proteins regulated proteolysis Microbiology QR1-502 Biswanath Jana Liang Tao Indranil Biswas Strain-Dependent Recognition of a Unique Degradation Motif by ClpXP in <named-content content-type="genus-species">Streptococcus mutans</named-content>
description	ABSTRACT Streptococcus mutans, a dental pathogen, has a remarkable ability to cope with environmental stresses. Under stress conditions, cytoplasmic proteases play a major role in controlling the stability of regulatory proteins and preventing accumulation of damaged and misfolded proteins. ClpXP, a well-conserved cytoplasmic proteolytic system, is crucial in maintaining cellular homeostasis in bacteria. ClpX is primarily responsible for recognition of substrates and subsequent translocation of unfolded substrates into the ClpP proteolytic compartment for degradation. In Escherichia coli, ClpX recognizes distinct motifs present at the C-terminal end of target proteins. However, recognition sequences for ClpXP in other bacteria, including S. mutans, are not known. In this study, using two-dimensional (2D) polyacrylamide gel electrophoresis (PAGE) analysis, we have identified several putative substrates for S. mutans ClpXP. SsbA, which encodes a small DNA binding protein, is one such substrate that is degraded by ClpXP. By sequential deletions, we found that the last 3 C-terminal amino acids, LPF, are sufficient for ClpXP-mediated degradation. Addition of LPF at the C-terminal end of green fluorescent protein (GFP) rendered the protein completely degradable by ClpXP. Alterations of this tripeptide motif impeded ClpXP-mediated degradation. However, recognition of LPF by ClpXP is highly specific to some S. mutans strains (UA159, UA130, and N3209) since not all S. mutans strains recognize the motif. We speculate that an adaptor protein is involved in either substrate recognition or substrate degradation by ClpXP. Nevertheless, this is the first report of a unique recognition sequence for ClpXP in streptococci. IMPORTANCE Regulated proteolysis in bacteria is an important biological process that maintains protein homeostasis. ClpXP, an intracellular proteolytic complex, is the primary protease that is responsible for protein turnover. While the substrates for ClpXP were identified in Escherichia coli, the substrates for vast majority of bacteria are currently unknown. In this study, we identified a unique substrate for ClpXP-mediated degradation in Streptococcus mutans, a dental pathogen. We also found that a small motif composed of 3 amino acids is sufficient for ClpXP-mediated degradation. Identification of this motif will clearly help us to understand the pathogenesis of this organism and other related pathogens.
format	article
author	Biswanath Jana Liang Tao Indranil Biswas
author_facet	Biswanath Jana Liang Tao Indranil Biswas
author_sort	Biswanath Jana
title	Strain-Dependent Recognition of a Unique Degradation Motif by ClpXP in <named-content content-type="genus-species">Streptococcus mutans</named-content>
title_short	Strain-Dependent Recognition of a Unique Degradation Motif by ClpXP in <named-content content-type="genus-species">Streptococcus mutans</named-content>
title_full	Strain-Dependent Recognition of a Unique Degradation Motif by ClpXP in <named-content content-type="genus-species">Streptococcus mutans</named-content>
title_fullStr	Strain-Dependent Recognition of a Unique Degradation Motif by ClpXP in <named-content content-type="genus-species">Streptococcus mutans</named-content>
title_full_unstemmed	Strain-Dependent Recognition of a Unique Degradation Motif by ClpXP in <named-content content-type="genus-species">Streptococcus mutans</named-content>
title_sort	strain-dependent recognition of a unique degradation motif by clpxp in <named-content content-type="genus-species">streptococcus mutans</named-content>
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/d92f84afab98425a834348f1c016d73e
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Strain-Dependent Recognition of a Unique Degradation Motif by ClpXP in <named-content content-type="genus-species">Streptococcus mutans</named-content>

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