McsA and the roles of metal-binding motif in Staphylococcus aureus

Abstract

McsA is a key modulator of stress response in Staphylococcus aureus that contains four CXXC potential metal binding motifs at the N-terminal. S. aureus ctsR operon encodes ctsR, clpC and putative mcsA and mcsB genes. The expression of the ctsR operon in S. aureus was shown to be induced in response to various types of heavy metals such as copper and cadmium. McsA was cloned and overexpressed, and purified product was tested for metal binding activity. The protein bound to Cu(II), Zn(II), Co(II) and Cd(II). No binding with any heavy metal except copper was found when we performed site directed mutagenesis of Cys residues of three CXXC motifs of McsA. These data suggest that two conserved cysteine ligands provided by one CXXC motif are required to bind copper ions. In addition, using a bacterial two-hybrid system, McsA was found to be able to bind to McsB and CtsR of S. aureus and the CXXC motif was needed for the binding. This indicates that the Cys residues in the CXXC motif are involved in metal binding and protein interaction.

The SAV1322 gene from Staphylococcus aureus: genomic and proteomic approaches to identification and characterization of gene function

“…MsrA2 reduces the S isomer of methionine sulfoxide, and MsrB reduces the R form, providing protection against oxidative stress [19]. In contrast, expression of ClpL, a protein involved in thermotolerance, was up-regulated in the sav1322 mutant strain.…”

“…Lastly, markedly lower expression levels of proteins involved in the stress response were observed in the sav1322 mutant, including the general stress protein 20U (Dps), methionine sulfoxide reductase A (MsrA2), and methionine sulfoxide reductase B (MsrB). MsrA2 reduces the S isomer of methionine sulfoxide, and MsrB reduces the R form, providing protection against oxidative stress [ 19 ]. In contrast, expression of ClpL, a protein involved in thermotolerance, was up-regulated in the sav1322 mutant strain.…”

Role of Adaptor TrfA and ClpPC in Controlling Levels of SsrA-Tagged Proteins and Antitoxins in Staphylococcus aureus

“…On the basis of homology to adaptors identified in Bacillus subtilis, there are at least three adaptors in S. aureus, namely, McsB (SA0482), YjbH (SA0860), and TrfA (SA0857). Studies have indicated the involvement of each in various stress responses (27)(28)(29), but many gaps remain in our understanding of the various roles played by these adaptors in S. aureus. Details of the protein targets of these S. aureus adaptors are limited, and to date, only two target proteins have been described to be regulated by S. aureus adaptors.…”

Understanding Stress Response to High-Arsenic Gold-Bearing Sulfide Concentrate in Extremely Metal-Resistant Acidophile Sulfobacillus thermotolerans

“…The ClpC subunit is required for growth at high temperatures (probably, it functions as a chaperone during heat shock) and for biofilm formation. It may act as a chaperone regulating CtsR activity [ 64 ] and participate in stress response to cadmium and copper ions [ 65 ]. In At.…”