Document Type

Article

Publication Date

2-14-2006

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

Department

Geisel School of Medicine

Abstract

The sarA locus in Staphylococcus aureus controls the expression of many virulence genes. The sarA regulatory molecule, SarA, is a 14.7-kDa protein (124 residues) that binds to the promoter region of target genes. Here we report the 2.6 Å-resolution x-ray crystal structure of the dimeric winged helix SarA protein, which differs from the published SarA structure dramatically. In the crystal packing, multiple dimers of SarA form a scaffold, possibly via divalent cations. Mutations of individual residues within the DNA-binding helix–turn–helix and the winged region as well as within the metal-binding pocket implicate basic residues R84 and R90 within the winged region to be critical in DNA binding, whereas acidic residues D88 and E89 (wing), D8 and E11 (metal-binding pocket), and cysteine 9 are essential for SarA function. These data suggest that the winged region of the winged helix protein participates in DNA binding and activation, whereas the putative divalent cation binding pocket is only involved in gene function.

DOI

10.1073/pnas.0510439103

Original Citation

Liu Y, Manna AC, Pan CH, Kriksunov IA, Thiel DJ, Cheung AL, Zhang G. Structural and function analyses of the global regulatory protein SarA from Staphylococcus aureus. Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2392-7. doi: 10.1073/pnas.0510439103. Epub 2006 Feb 2. PMID: 16455801; PMCID: PMC1413715.

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