Publication details for Dr Karrera DjokoCouñago, Rafael M., Chen, Nathan H., Chang, Chiung-Wen, Djoko, Karrera Y., McEwan, Alastair G. & Kobe, Bostjan (2016). Structural basis of thiol-based regulation of formaldehyde detoxification in H. influenzae by a MerR regulator with no sensor region. Nucleic Acids Research 44(14): 6981-6993.
- Publication type: Journal Article
- ISSN/ISBN: 0305-1048 (print), 1362-4962 (electronic)
- DOI: 10.1093/nar/gkw543
- Further publication details on publisher web site
- Durham Research Online (DRO) - may include full text
Author(s) from Durham
Pathogenic bacteria such as Haemophilus influenzae, a major cause of lower respiratory tract diseases, must cope with a range of electrophiles generated in the host or by endogenous metabolism. Formaldehyde is one such compound that can irreversibly damage proteins and DNA through alkylation and cross-linking and interfere with redox homeostasis. Its detoxification operates under the control of HiNmlR, a protein from the MerR family that lacks a specific sensor region and does not bind metal ions. We demonstrate that HiNmlR is a thiol-dependent transcription factor that modulates H. influenzae response to formaldehyde, with two cysteine residues (Cys54 and Cys71) identified to be important for its response against a formaldehyde challenge. We obtained crystal structures of HiNmlR in both the DNA-free and two DNA-bound forms, which suggest that HiNmlR enhances target gene transcription by twisting of operator DNA sequences in a two-gene operon containing overlapping promoters. Our work provides the first structural insights into the mechanism of action of MerR regulators that lack sensor regions.