This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Li, R.
Right arrow Articles by Zhang, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, R.
Right arrow Articles by Zhang, G.

 Previous Article  |  Next Article 

Journal of Bacteriology, July 2003, p. 4219-4225, Vol. 185, No. 14
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.14.4219-4225.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Crystal Structure of the SarS Protein from Staphylococcus aureus

Ronggui Li,1,{dagger} Adhar C. Manna,2 Shaodong Dai,1 Ambrose L. Cheung,2 and Gongyi Zhang1*

Integrated Department of Immunology, National Jewish Medical and Research Center, and Department of Pharmacology, Biomolecular Structure Program, School of Medicine, University of Colorado Health Science Center, Denver, Colorado 80206,1 Departments of Microbiology and Immunology, Dartmouth Medical School, Hanover, New Hampshire 037552

Received 3 February 2003/ Accepted 28 April 2003

The expression of virulence determinants in Staphylococcus aureus is controlled by global regulatory loci (e.g., sarA and agr). One of these determinants, protein A (spa), is activated by sarS, which encodes a 250-residue DNA-binding protein. Genetic analysis indicated that the agr locus likely mediates spa repression by suppressing the transcription of sarS. Contrary to SarA and SarR, which require homodimer formation for proper function, SarS is unusual within the SarA protein family in that it contains two homologous halves, with each half sharing sequence similarity to SarA and SarR. Here we report the 2.2 Å resolution X-ray crystal structure of the SarS protein. SarS has folds similar to those of SarR and, quite plausibly, the native SarA structure. Two typical winged-helix DNA-binding domains are connected by a well-ordered loop. The interactions between the two domains are extensive and conserved. The putative DNA-binding surface is highly positively charged. In contrast, negatively charged patches are located opposite to the DNA-binding surface. Furthermore, sequence alignment and structural comparison revealed that MarR has folds similar to those of SarR and SarS. Members of the MarR protein family have previously been implicated in the negative regulation of an efflux pump involved in multiple antibiotic resistance in many gram-negative species. We propose that MarR also belongs to the winged-helix protein family and has a similar mode of DNA binding as SarR and SarS and possibly the entire SarA protein family member. Based on the structural differences of SarR, SarS, and MarR, we further classified these winged-helix proteins to three subfamilies, SarA, SarS, and MarR. Finally, a possible transcription regulation mechanism is proposed.

* Corresponding author. Mailing address: 1400 Jackson St. K405, Denver, CO 80206. Phone: (303) 398-1715. Fax: (303) 398-1396. E-mail: zhangg{at}njc.org.

{dagger} Present address: University of Qingdao, Qingdao, People's Republic of China.

Journal of Bacteriology, July 2003, p. 4219-4225, Vol. 185, No. 14
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.14.4219-4225.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ballal, A., Manna, A. C. (2009). Expression of the sarA family of genes in different strains of Staphylococcus aureus. Microbiology 155: 2342-2352 [Abstract] [Full Text]  
  • Chu, H. W., Thaikoottathil, J., Rino, J. G., Zhang, G., Wu, Q., Moss, T., Refaeli, Y., Bowler, R., Wenzel, S. E., Chen, Z., Zdunek, J., Breed, R., Young, R., Allaire, E., Martin, R. J. (2007). Function and Regulation of SPLUNC1 Protein in Mycoplasma Infection and Allergic Inflammation. J. Immunol. 179: 3995-4002 [Abstract] [Full Text]  
  • Manna, A. C., Cheung, A. L. (2006). Expression of SarX, a Negative Regulator of agr and Exoprotein Synthesis, Is Activated by MgrA in Staphylococcus aureus.. J. Bacteriol. 188: 4288-4299 [Abstract] [Full Text]  
  • Liu, Y., Manna, A. C., Pan, C.-H., Kriksunov, I. A., Thiel, D. J., Cheung, A. L., Zhang, G. (2006). Structural and function analyses of the global regulatory protein SarA from Staphylococcus aureus. Proc. Natl. Acad. Sci. USA 103: 2392-2397 [Abstract] [Full Text]  
  • Tran, H. J., Heroven, A. K., Winkler, L., Spreter, T., Beatrix, B., Dersch, P. (2005). Analysis of RovA, a Transcriptional Regulator of Yersinia pseudotuberculosis Virulence That Acts through Antirepression and Direct Transcriptional Activation. J. Biol. Chem. 280: 42423-42432 [Abstract] [Full Text]  
  • De Silva, R. S., Kovacikova, G., Lin, W., Taylor, R. K., Skorupski, K., Kull, F. J. (2005). Crystal Structure of the Virulence Gene Activator AphA from Vibrio cholerae Reveals It Is a Novel Member of the Winged Helix Transcription Factor Superfamily. J. Biol. Chem. 280: 13779-13783 [Abstract] [Full Text]  
  • Manna, A. C., Ingavale, S. S., Maloney, M., van Wamel, W., Cheung, A. L. (2004). Identification of sarV (SA2062), a New Transcriptional Regulator, Is Repressed by SarA and MgrA (SA0641) and Involved in the Regulation of Autolysis in Staphylococcus aureus. J. Bacteriol. 186: 5267-5280 [Abstract] [Full Text]  
  • Gao, J., Stewart, G. C. (2004). Regulatory Elements of the Staphylococcus aureus Protein A (Spa) Promoter. J. Bacteriol. 186: 3738-3748 [Abstract] [Full Text]  
  • McCallum, N., Bischoff, M., Maki, H., Wada, A., Berger-Bachi, B. (2004). TcaR, a Putative MarR-Like Regulator of sarS Expression. J. Bacteriol. 186: 2966-2972 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»