Abstract
HapR is a TetR-family transcriptional regulator that controls quorum sensing in Vibrio cholerae, the causative agent of cholera. HapR regulates the expression of hemagglutinin protease, virulence and biofilm genes. The crystal structure of wild-type HapR from V. cholerae strain O1 El Tor C6706 has previously been solved. In this study, the structure of a DNA-binding-deficient variant of HapR (HapRV2) derived from the protease-deficient V. cholerae serotype O37 strain V2 is reported. The structure reveals no structural differences compared with wild-type HapR. However, structural alignment of HapRV2 with the TetR-family member QacR in complex with its operator DNA suggests that the aspartate residue located between the regulatory and DNA-binding domains may clash with and electrostatically repel the phosphate backbone of DNA to prevent binding.
Highlights
The acute diarrheal disease cholera is caused by ingesting food or water contaminated with the Gram-negative bacterium Vibrio cholerae
Toxigenic V. cholerae causes disease by producing two primary virulence factors: cholera toxin (CT) and the toxincoregulated pilus (TCP) (Taylor et al, 1987). The expression of these virulence factors is controlled by a network of transcriptional regulators that is initiated when AphA cooperates with AphB to activate the expression of TcpPH (Skorupski & Taylor, 1999; DiRita et al, 1991; Kovacikova & Skorupski, 1999; Kovacikova et al, 2004, 2010)
The crystal structure of HapRV2 was refined to a resolution of 2.1 A (Fig. 1)
Summary
The acute diarrheal disease cholera is caused by ingesting food or water contaminated with the Gram-negative bacterium Vibrio cholerae. Toxigenic V. cholerae causes disease by producing two primary virulence factors: cholera toxin (CT) and the toxincoregulated pilus (TCP) (Taylor et al, 1987) The expression of these virulence factors is controlled by a network of transcriptional regulators that is initiated when AphA cooperates with AphB to activate the expression of TcpPH (Skorupski & Taylor, 1999; DiRita et al, 1991; Kovacikova & Skorupski, 1999; Kovacikova et al, 2004, 2010). V. cholerae uses quorum sensing to regulate gene expression in response to an increase in cell density (Miller & Bassler, 2001). Strain V2 was recently found to contain a glycine-to-aspartate substitution at position 39 within the hinge region between the DNA-binding and dimerization domains of HapR (HapRV2; Dongre et al, 2011). 96.92 2.82 0.26 0.00 10.5 statically repel DNA, preventing the binding and the regulation of genes controlled by the quorum-sensing system of V. cholerae
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