Crystal structure of the SarR protein from Staphylococcus aureus

The expression of virulence determinants in Staphylococcos aureus is contro lled by global regulatory loci (e,g., sarA and agr), The sar (Staphylococcu s accessory regulator) locus is composed of three overlapping transcripts ( sarA P1, P3, and P2, transcripts initiated from the P1, P3, and P2 promoter s, respectively), all encoding the 124-aa sarA protein. The level of SarA, the major regulatory protein, is partially controlled by the differential a ctivation of the sarA promoters. We previously partially purified a 13.6-kD a protein, designated sarR, that binds to the sarA promoter region to down- modulate sarA transcription from the pi promoter and subsequently SarA expr ession. SarR shares sequence similarity to SarA, and another SarA homolog, Sars. Here we report the 2.3 A-resolution x-ray crystal structure of the di meric SarR-MBP (maltose binding protein) fusion protein. The structure reve als that the SarR protein not only has a classic helix-turn-helix module fo r DNA binding at the major grooves, but also has an additional loop region involved in DNA recognition at the minor grooves. This interaction mode cou ld represent a new functional class of the "winged helix" family. The dimer ic SarR structure could accommodate an unusually long stretch of approximat e to 27 nucleotides with two or four bending points along the course, which could lead to the bending of DNA by 90 degrees or more, similar to that se en in the catabolite activator protein (CAP)-DNA complex. The structure als o demonstrates the molecular basis for the stable dimerization of the sarR monomers and possible motifs for interaction with other proteins.