Crystal Structure of Enterococcus faecalis SlyA-like Transcriptional Factor

Abstract

The crystal structure of a SlyA transcriptional regulator at 1.6 Å resolution is presented, and structural relationships between members of the MarR/SlyA family are discussed. The SlyA family, which includes SlyA, Rap, Hor, and RovA proteins, is widely distributed in bacterial and archaeal genomes. Current evidence suggests that SlyA-like factors act as repressors, activators, and modulators of gene transcription. These proteins have been shown to up-regulate the expression of molecular chaperones, acid-resistance proteins, and cytolysin, and down-regulate several biosynthetic enzymes. The structure of SlyA from Enterococcus faecalis, determined as a part of an ongoing structural genomics initiative (www.mcsg.anl.gov), revealed the same winged helix DNA-binding motif that was recently found in the MarR repressor from Escherichia coli and the MexR repressor from Pseudomonas aeruginosa, a sequence homologue of MarR. Phylogenetic analysis of the MarR/ SlyA family suggests that Sly is placed between the SlyA and MarR subfamilies and shows significant sequence similarity to members of both subfamilies.

Critical biophysical properties in the Pseudomonas aeruginosa efflux gene regulator MexR are targeted by mutations conferring multidrug resistance

“…Indeed, the dimeric state of proteins in the MarR family is well-documented both biophysically 32 and structurally. [9][10][11][12]14 All mutants in this study maintain a near-native secondary structure content, which would be hard to conceptualize for a monomeric state, considering the intertwined helices in the dimer region [ Fig. 1(A)].…”

“…1,[6][7][8] Several structures of members in the MarR family have shed light on their structural properties and possible mechanisms for DNA-recognition. [9][10][11][12][13][14] MexR from the pathogen Pseudomonas aeruginosa belongs to this fold family, where two winged-helixturn-helix (wHTH) domains are linked by a dimer core formed by four interacting helices N-and C-terminal to the wHTH domains [ Fig. 1(A)].…”

Identification of amino acid residues of Salmonella SlyA that are critical for transcriptional regulation

“…These regulatory proteins control the expression of resistance to multiple antibiotics, organic solvents, agents that induce oxidative stress, and virulence factors (Alekshun & Levy, 1997). This diverse group of MarR homologues is very similar with respect to protein structure; the protein forms a dimer and contains a wingedhelix DNA-binding motif (Alekshun et al, 2001;De Silva et al, 2005;Hong et al, 2005;Lim et al, 2002;Liu et al, 2001;Wu et al, 2003). In these regulatory proteins, the helix-turn-helix motif is followed by a wing composed of two antiparallel b-strands.…”

“…SlyA is known as a member of the MarR/SlyA family of transcription regulators, more than 130 of which have been identified thus far in bacteria and archaea (Thomson et al, 1997;Wu et al, 2003). , 2004).…”

“…Interestingly, several of these SlyAactivated genes were also controlled by the PhoP/PhoQ twocomponent regulatory system, including those genes required for virulence and resistance to antimicrobial peptides (Navarre et al, 2005). In addition, slyA itself is activated under low-Mg 2+ conditions by the PhoP protein, which binds directly to the slyA promoter region (Norte et al, 2003;Shi et al, 2004).SlyA is known as a member of the MarR/SlyA family of transcription regulators, more than 130 of which have been identified thus far in bacteria and archaea (Thomson et al, 1997;Wu et al, 2003). , 2004).…”