Degradation of the E. coli antitoxin MqsA by the proteolytic complex ClpXP is regulated by zinc occupancy and oxidation

Abstract

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Single-cell analysis reveals that cryptic prophage protease LfgB protects Escherichia coli during oxidative stress by cleaving antitoxin MqsA

“…As previously demonstrated, Lon protease can degrade MqsA as well as other antitoxins under oxidative stress ( 12 ). In addition, ClpXP degrades MqsA in the absence of zinc that is used to stabilize the structure of MqsA, that is, when it is unfolded ( 52 ). It was proposed that the ClpX recognition site is accessible under non-stress conditions; however, under oxidative conditions, cysteine residues are oxidized, preventing the correct folding and the binding of zinc and allowing ClpXP to degrade MqsA ( 52 ).…”

“…In addition, ClpXP degrades MqsA in the absence of zinc that is used to stabilize the structure of MqsA, that is, when it is unfolded ( 52 ). It was proposed that the ClpX recognition site is accessible under non-stress conditions; however, under oxidative conditions, cysteine residues are oxidized, preventing the correct folding and the binding of zinc and allowing ClpXP to degrade MqsA ( 52 ). Hence, our results with protease LfgB provide additional evidence for the selective degradation of free antitoxins under stress conditions ( 12 , 29 , 52 ).…”

Single-Cell Analysis Reveals Cryptic Prophage Protease LfgB ProtectsEscherichia coliDuring Oxidative Stress by Cleaving Antitoxin MqsA

“…In addition, ClpXP degrades MqsA in the absence of the zinc that is used to stabilize the structure of MqsA; i.e., when it is unfolded 50 . It was proposed that the ClpX recognition site is accessible under non-stress conditions; however, under oxidative conditions, cysteine residues are oxidized preventing the correct folding and the binding of zinc, allowing ClpXP to degrade MqsA 50 . Hence, our results with protease LfgB provide additional evidence for the selective degradation of free antitoxins under stress conditions 30, 50, 51 .…”

“…In the absence of stress, one physiological role of MqsA is to inhibit rpoS transcription 51 , which is important for rapid growth. However, under stress conditions (H 2 O 2 , acid, heat), Lon protease 51 , ClpXP protease 50 , and LfgB protease degrade antitoxin MqsA, facilitating the formation of RpoS and activation of the stress response. This also shifts the balance to MqsR 39, 51 , which then performs differential mRNA decay 23 , based on the presence of single-stranded, 5’-GCU sites 8 .…”

“…As previously demonstrated, Lon protease can degrade MqsA as well as other antitoxins under oxidative stress 51 . In addition, ClpXP degrades MqsA in the absence of the zinc that is used to stabilize the structure of MqsA; i.e., when it is unfolded 50 . It was proposed that the ClpX recognition site is accessible under non-stress conditions; however, under oxidative conditions, cysteine residues are oxidized preventing the correct folding and the binding of zinc, allowing ClpXP to degrade MqsA 50 .…”