Crystal structures of SarA, a pleiotropic regulator of virulence genes in S. aureus (vol 409, pg 215, 2001)

[摘要] Staphylococcus 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(1-3). 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(4). Subsequent DNA-binding studies have revealed that SarA binds readily to multiple AT-rich sequences of variable lengths(4-11). Here we describe the crystal structure of SarA and a SarA-DNA complex at resolutions of 2.50 Angstrom and 2.95 Angstrom, 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.

[关键词] STAPHYLOCOCCUS-AUREUS;LOCUS SAR;AGR;TRANSCRIPTION;DIFFRACTION;EXPRESSION