Abstract
Bordetella bacteria are respiratory pathogens of humans, birds, and livestock. Bordetella pertussis the causative agent of whopping cough remains a significant health issue. The transcriptional regulator, BpsR, represses a number of Bordetella genes relating to virulence, cell adhesion, cell motility, and nicotinic acid metabolism. DNA binding of BpsR is allosterically regulated by interaction with 6-hydroxynicotinic acid (6HNA), the first product in the nicotinic acid degradation pathway. To understand the mechanism of this regulation, we have determined the crystal structures of BpsR and BpsR in complex with 6HNA. The structures reveal that BpsR binding of 6HNA induces a conformational change in the protein to prevent DNA binding. We have also identified homologs of BpsR in other Gram negative bacteria in which the amino acids involved in recognition of 6HNA are conserved, suggesting a similar mechanism for regulating nicotinic acid degradation.
Highlights
Bordetella bacteria are Gram-negative, respiratory pathogens of humans, birds, and animal livestock
The two wHtH motifs are positioned in tandem to one another to create a DNA binding surface (Fig 1)
The overall structure of the dimer is similar to other members of the MarR family of transcriptional regulators [33,34,35,36,37]
Summary
Bordetella bacteria are Gram-negative, respiratory pathogens of humans, birds, and animal livestock. The BpsR proteins from the three classical Bordetella species exhibit >99% amino acid sequence identity [15]. These structures reveal a conformational change in protein structure upon BpsR binding of 6HNA that make it incompatible with DNA binding and explain the allosteric regulation.
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