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

Crystal Structure of the SarS Protein from Staphylococcus aureus

Ronggui Li,^1, Adhar C. Manna,² Shaodong Dai,¹ Ambrose L. Cheung,² and Gongyi Zhang^1*

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.

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

This article has been cited by other articles:

• 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]