Molecular Insights into the Impact of Oxidative Stress on the Quorum-Sensing Regulator Protein LasR

Content Provider	Scilit
Author	Kafle, Prapti Amoh, Amanda N. Reaves, Jocelyn M. Suneby, Emma G. Tutunjian, Kathryn A. Tyson, Reed L. Schneider, Tanya L.
Copyright Year	2016
Description	Journal: Journal of Biological Chemistry The LasR regulator protein functions at the top of the Pseudomonas aeruginosa quorum-sensing hierarchy and is implicated in promoting bacterial virulence. Of note is recent evidence that this transcription factor may also respond to oxidative stress. Here, all cysteines in LasR were inspected to deduce their redox sensitivity and to probe the connection between stress response and LasR activity using purified LasR and individual LasR domains. $Cys^{79}$ in the ligand binding domain of LasR appears to be important for ligand recognition and folding of this domain to potentiate DNA binding but does not seem to be sensitive to oxidative stress when bound to its native ligand. Two cysteines in the DNA binding domain of LasR do form a disulfide bond when treated with hydrogen peroxide, and formation of this $Cys^{201}-Cys^{203}$ disulfide bond appears to disrupt the DNA binding activity of the transcription factor. Mutagenesis of either of these cysteines leads to expression of a protein that no longer binds DNA. A cell-based reporter assay linking LasR function with β-galactosidase activity gave results consistent with those obtained with purified LasR. This work provides a possible mechanism for oxidative stress response by LasR and indicates that multiple cysteines within the protein may prove to be useful targets for disabling its activity.
Related Links	http://www.jbc.org/content/291/22/11776.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882445/pdf http://www.jbc.org/article/S0021925820432077/pdf
Ending Page	11786
Page Count	11
Starting Page	11776
ISSN	00219258
e-ISSN	1083351X
DOI	10.1074/jbc.m116.719351
Journal	Journal of Biological Chemistry
Issue Number	22
Volume Number	291
Language	English
Publisher	Elsevier BV
Publisher Date	2016-05-01
Access Restriction	Open
Subject Keyword	Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Dna Binding Protein Pseudomonas Aeruginosa Antibiotic Resistance Bacterial Pathogenesis Bacterial Transcription Ligand-binding Protein Quorum Sensing
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology