RegulonDB RegulonDB RegulonDB 8.8: Gensor Unit


Sigma24 Genetic Sensory Response Unit in Escherichia coli K-12 genome


 
Reactions
R1
R2
R3
R4
R5
R6
R7
R8
R9

SUMMARY: In the absence of stress, the sigma factor σ24 is complexed with RssA and RssB in the inner membrane, but under envelope stress, misfolded proteins and lipoproteins appear in the periplasm. The lipoproteins release RssB from the complex RssB-rseA-σ24, and then a proteolytic cascade starts when DegS, bound to unfolded proteins, partially degrades the RseA protein in the RseA-σ24 complex, producing the RseA-1-108 polypeptide that is cleaved by RseP, and the complex is released from the inner membrane. In the cytoplasm, HslUV or Lon can degrade RseA, releasing σ24, which can bind to core RNA polymerase to activate transcription of genes for maintaining cell envelope integrity. Another protease that also degrades RseA in the cytoplasm is ClpXP, but the protein SspB has to be bound to the RseA-1-108-RpoE complex. On the other hand, the rpoE gene, which forms part of the rpoE-rseAB operon, is induced by the TF CpxR, which is shown in the image as a submap in a gray box.


CpxR p1-p2 rpoE-rseABC DegS RseA RseP RseB Sigma24 rpoE-rseABC_mRNA RseC core-RNAP Genes for maintaining cell envelope integrity mRNAs for maintaining cell envelope integrity OMP Sigma24 core-RNAP Sigma24 RseA OMP DegS RseB lipoprotein Sigma24 RseA lipoprotein RseB Sigma24 RseA Sigma24 RseA RseA ClpXP Sigma24 RseA SspB SspB Lon Envelope Stress HslUV
REACTION DESCRIPTION Info
Reaction # R1
Reaction name RseB+RseA+Sigma24->RseA-RseB-Sigma24
Reaction description Complex formation to inhibit the Sigma24 activity
Reaction type Inhibition by binding
Reactant1 name RseB
Reactant1 type Anti-sigma factor
Reactant2 name RseA
Reactant2 ype Anti-sigma factor
Reactant3 name Sigma24
Reactant3 type Sigma factor
Product name RseB-RseA-Sigma24
Growth condition under which the reaction is inactive Envelope stress
Evidence IPI coimmunoprecipitation assay [11777003]
IPI cocrystallization [20512978, 17496148, 17692869]
IPI size-exclusion chromatography [17692869]
IPI cross-linking [17692869]
References PubMed: 11777003 20512978 17692869
Comments RseA and Sigma24 can form a complex without RseB; however, RseB increases the affinity of RseA for Sigma24 [11777003].In the RseB- RseA-Sigma24 complex, RseB blocks access of the DegS protease to the RseA protein [20512978].RseA is completly inserted in the inner membrane, and its N-terminal domain, which is located in the cytoplasm, binds to Sigma24 to prevent transcription by Sigma24-RNAP. The C terminal of RseA , which is located in the periplasm, does contact the RseB protein, which blocks access of the proteases to RseA [20512978].
Reaction # R2
Reaction name Lipoprotein (mislocalized)+RseB-RseA-Sigma24->lipoprotein-RseB+RseA-Sigma24
Reaction description Mislocalized protein traps RseB from the RseB-RseA-Sigma24 complex; start of proteolytic cascade
Reaction type Inhibition by binding
Reactant1 name Lipoprotein (mislocalized)
Reactant1 type Lipoprotein
Reactant2 name RseB-RseA-Sigma24
Reactant2 type Protein complex
Product1 name Lipoprotein (mislocalized)-RseB
Product2 name RseA-Sigma24
Growth condition under which the reaction is active Envelope stress
Evidence HINF human inference of function from structure [17692869]
References PubMed: 17692869
Comments Wollman et al. proposed tha RseB recognizes and binds to mislocalized protein and that this binding causes a conformational change in RseB, destabilizing the binding of this protein with RseA [17692869].
Reaction # R3
Reaction name DegS+OMP[unfolded]->DegS-OMP
Reaction description Activation of DegS by unfolded membrane proteins
Reaction type Activation by binding
Reactant1 name DegS (inactive)
Reactant type Protease
Reactant2 name OMP (unfolded)
Reactant type OMP (unfolded)
Product name DegS-OMP (unfolded)
Growth condition under which the reaction is active Envelope stress
Evidence IPI affinity chromatography [12679035 ]
IMP reaction blocked in mutant [12679035, 15137941 ]
IPI cocrystallization [15137941]
IDA in vitro proteolysis reconstitution assay [12183369, 12679035, 15137941, 17981123]
References PubMed: 12679035 17981123 15137941
Comments The cooperative binding of unfolded outer membrane porins (OMPs) to the autoinhibitory PDZ domain of DegS allosterically activates DegS as a protease. The C termini of OMPs bind to this domain [15137941, 12679035, 15520285]. The activation of DegS is a reversible reaction [15137941].
Reaction # R4
Reaction name RseA-Sigma24->RseA[1-148]-Sigma24
Reaction description DegS cleavages at site 1 of RseA
Reaction type Proteolysis
Reactant name RseA-Sigma24
Reactant type Protein complex
Product name RseA[1-148]-Sigma24
Catalyst name DegS-OMP
Catalyst type Complex
Growth condition under which the reaction is active Envelope stress
Evidence IDA in vitro proteolysis reconstitution assay [12183369, 12679035, 15137941, 17981123 ]
References PubMed: 12183369 12679035
Reaction # R5
Reaction name RseA[1-148]-Sigma24->RseA[1-108]-Sigma24
Reaction description RseP cleavages at site 2 of RseA
Reaction type Proteolysis
Reactant name RseA[1-148]-Sigma24
Reactant type Anti-sigma factor
Product name RseA[1-108]-Sigma24
Catalyst name RseP
Catalyst type Protease
Growth condition under which the reaction is active Envelope stress
Evidence IMP reaction blocked in mutant [12183369, 19706448 ]
IDA in vitro proteolysis reconstitution assay [12183369 ]
References PubMed: 12183369 19706448
Comments DegS-dependent cleavage of RseA is a prerequisite for cleavage by RseP [19706448]. Two Gln-rich regions in the periplasmic domain of RseA inhibit RseP from cleaving the intact RseA. RseA lacking these regions is susceptible to cleavage by RseP [14633997].
Reaction # R6
Reaction name SspB+RseA[1-108]-Sigma24->SspB-RseA[1-108]-Sigma24
Reaction description Targgeting for proteolysis to RseA[1-108] by SspB
Reaction type Targeting for proteolysis
Reactant name SspB+RseA[1-108]-Sigma24
Reactant type Protein complex
Reactant name SspB
Reactant type Proteolysis targeting factor
Product1 name RssB-RseA[1-108]-Sigma24
Evidence IPI gel filtration [15371343]
IMP reaction blocked in mutant [15371343]
IDA in vitro proteolysis reconstitution assay [15371343]
IPI cocrystallization [15880122]
References PubMed: 15371343 15880122
Comments SspB targets RseA for degradation [15371343].
Reaction # R7
Reaction name SspB-RseA[1-108]-Sigma24->RseA (degraded)+ Sigma24+SspB
Reaction description ClpXP degrades RseA[1-108], and SspB and Sigma24 are released
Reaction type Proteolysis
Reactant name SspB-RseA[1-108]-Sigma24
Reactant type Protein complex
Product1 name Sigma24
Product2 name RseA (degraded)
Product3 name SspB
Catalyst name ClpXP
Catalyst type Protease
Growth condition under which the reaction is active Envelope stress
Evidence IDA in vitro proteolysis reconstitution assay [17210793, 15371343]
IDA in vivo proteolysis analysis [17210793]
IMP reaction blocked in mutant [15371343]
References PubMed: 15371343 17210793
Comments ClpXP is the major protease for RseA degradation; however, other proteases contribute to lesser extents in the degradation of the sigma factor [17210793]. ClpXP degrade RseA[1-108], resulting in the release of SspB and Sigma24 [15371343, 17210793].
Reaction # R8
Reaction name RseA[1-108]-Sigma24->RseA(degraded)+ Sigma24
Reaction description Lon or HslUV degrades RseA[1-108], Sigma24 is released
Reaction type Proteolysis
Reactant name RseA[1-108]-Sigma24
Reactant type Protein complex
Product1 name Sigma24
Product2 name RseA (degraded)
Catalyst name Lon
Catalyst type Protease
Catalyst2 name HslUV
Growth condition under which the reaction is active Envelope stress
Evidence IDA in vitro proteolysis reconstitution assay [17210793]
IDA in vivo proteolysis analysis [17210793]
References PubMed: 17210793
Comments ClpXP is the major protease of Sigma24; however, Lon and HslUV contribute to lesser extents in the degradation of the sigma factor [17210793].Lon and HslUV destroy only to RseA in the RseA[1-108]-Sigma24 complex, and Sigma24 is released from the complex during the proteolysis reaction.HslUV degrades RseA in vivo, but not in vitro. Other proteases proved to degrade CpxA are ClpAP, which works in vitro but not in vivo, and FtsH, which hardly works in vitro (it was not possible to determine its effect in vivo) [17210793].
Reaction # R9
Reaction name Core-RNAP+Sigma24->core-RNAP-Sigma24
Reaction description Binding of core-RNAP with Sigma24
Reaction type Activation by binding
Reactant1 name Core-RNAP
Reactant1 type Protein complex
Reactant2 name Sigma24
Reactant2 type Sigma factor
Product name Core-RNAP-Sigma24
Growth condition under which the reaction is active Envelope stress
Evidences IPI coimmunoprecipitation assay [11777003]
IPI affinity chromatography [11777003]
References PubMed: 11777003
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