Structural insight into the oxidation-sensing mechanism of the antibiotic resistance of regulator MexR.
MexR functions as the primary regulator of the mexAB-oprM multidrug efflux expression in Pseudomonas aeruginosa. It has been shown that MexR senses oxidative stress by interprotomer disulphide bond formation between redox-active cysteines. This oxidation induces MexR to dissociate from the promoter DNA, thus activating the transcriptional expression of efflux pump genes. In this study, we present the crystal structure of MexR in its oxidized form at a resolution of 2.1 A. This crystal structure reveals the mechanism by which oxidative signal allosterically derepresses the MexR-controlled transcription activation.
Chen
Hao
H
Coordination Chemistry Institute and the State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Hankou Road, Nanjing 210093, People's Republic of China. chenhao@nju.edu.cn
Yi
Chengqi
C
Zhang
Jin
J
Zhang
Wenru
W
Ge
Zhiyun
Z
Yang
Cai-Guang
CG
He
Chuan
C
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry; D004352:Drug Resistance, Microbial; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011401:Promoter Regions, Genetic; D017510:Protein Folding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
D001426:Bacterial Proteins; D004220:Disulfides; C423620:MexR protein, Pseudomonas aeruginosa; D012097:Repressor Proteins