7ve5
C-terminal domain of VraRC-terminal domain of VraR
Structural highlights
FunctionVRAR_STAA8 Member of the two-component regulatory system VraS/VraR involved in the control of the cell wall peptidoglycan biosynthesis. Upon cellular stress, the histidine kinase VraS transfers the phosphoryl group onto VraR. Upon phosphorylation, VraR dimerizes at the N-terminal domain. In turn, phosphorylation-induced dimerization expand and enhance the VraR binding to its own promoter leading to increased expression and subsequent modulation of as many as 40 genes, which ultimately constitute the S.aureus response to cell wall damage (PubMed:31277575). In addition, inhibits the host autophagic flux and delays the early stage of autophagosome formation, thereby promoting bacterial survival. Facilitates the ability of S.aureus to resist host polymorphonuclear leukocytes-mediated phagocytosis and killing thus contributing to immune evasion (By similarity).[UniProtKB:Q9KWK8][1] Publication Abstract from PubMedIn Staphylococcus aureus, vancomycin-resistance-associated response regulator (VraR) is a part of the VraSR two-component system, which is responsible for activating a cell wall-stress stimulon in response to an antibiotic that inhibits cell wall formation. Two VraR-binding sites have been identified: R1 and R2 in the vraSR operon control region. However, the binding of VraR to a promoter DNA enhancing downstream gene expression remains unclear. VraR contains a conserved N-terminal receiver domain (VraRN ) connected to a C-terminal DNA binding domain (VraRC ) with a flexible linker. Here, we present the crystal structure of VraRC alone and in complex with R1-DNA in 1.87- and 2.0-A resolution, respectively. VraRC consisting of four alpha-helices forms a dimer when interacting with R1-DNA. In the VraRC -DNA complex structure, Mg(2+) ion is bound to Asp194. Biolayer interferometry experiments revealed that the addition of Mg(2+) to VraRC enhanced its DNA binding affinity by eightfold. In addition, interpretation of NMR titrations between VraRC with R1- and R2-DNA revealed the essential residues that might play a crucial role in interacting with DNA of the vraSR operon. The structural information could help in designing and screening potential therapeutics/inhibitors to deal with antibiotic-resistant S. aureus via targeting VraR. Structural insights into DNA binding domain of vancomycin-resistance-associated response regulator in complex with its promoter DNA from Staphylococcus aureus.,Kumar JV, Tseng TS, Lou YC, Wei SY, Wu TH, Tang HC, Chiu YC, Hsu CH, Chen C Protein Sci. 2022 May;31(5):e4286. doi: 10.1002/pro.4286. PMID:35481641[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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