1fzp
From Proteopedia
CRYSTAL STRUCTURES OF SARA: A PLEIOTROPIC REGULATOR OF VIRULENCE GENES IN S. AUREUS
Structural highlights
Function[SARA_STAAU] Global regulator with both positive and negative effects that controls expression of several virulence factors and biofilm formation process in a cell density-dependent manner. In a strain-dependent manner plays a role in multidrug resistance mechanism. Is required for transcription of primary transcripts RNAII and RNAIII generated by agr (virulence accessory gene regulator) locus. Acts as a transcriptional activator of the genes encoding, among others, for fibronectin binding proteins (fnbA and fnbB), hemolysins (hla, hld, hlgB and hlgC), serine proteases (splA, splB, splD and splF) and of the bap gene, which is essential for biofilm development in some strains. Negatively regulates the expression of the genes for protein A (spa), lipase (lip), thermonuclease (nuc), immunodominant staphylococcal antigen B (isaB), staphylococcal serine and cysteine proteases (sspA and sspB), staphostatin B (sspC), metalloprotease aureolysin (aur) and collagen adhesin (cna). Probably activates the development of biofilm by both enhancing the ica operon transcription and suppressing the transcription of either a protein involved in the turnover of PIA/PNAG or a repressor of its synthesis, whose expression would be sigma-B-dependent.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedStaphylococcus aureus is a major human pathogen, the potency of which can be attributed to the regulated expression of an impressive array of virulence determinants. A key pleiotropic transcriptional regulator of these virulence factors is SarA, which is encoded by the sar (staphylococcal accessory regulator) locus. SarA was characterized initially as an activator of a second virulence regulatory locus, agr, through its interaction with a series of heptad repeats (AGTTAAG) within the agr promoter. Subsequent DNA-binding studies have revealed that SarA binds readily to multiple AT-rich sequences of variable lengths. Here we describe the crystal structure of SarA and a SarA-DNA complex at resolutions of 2.50 A and 2.95 A, respectively. SarA has a fold consisting of a four-helix core region and 'inducible regions' comprising a beta-hairpin and a carboxy-terminal loop. On binding DNA, the inducible regions undergo marked conformational changes, becoming part of extended and distorted alpha-helices, which encase the DNA. SarA recognizes an AT-rich site in which the DNA is highly overwound and adopts a D-DNA-like conformation by indirect readout. These structures thus provide insight into SarA-mediated transcription regulation. Crystal structures of SarA, a pleiotropic regulator of virulence genes in S. aureus.,Schumacher MA, Hurlburt BK, Brennan RG Nature. 2001 Jan 11;409(6817):215-9. PMID:11196648[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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