Structural basis of thiol-based regulation of formaldehyde detoxification in H. influenzae by a MerR regulator with no sensor region

Couñago, Rafael M., Chen, Nathan H., Chang, Chiung-Wen, Djoko, Karrera Y., McEwan, Alastair G. and 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. doi:10.1093/nar/gkw543


Author Couñago, Rafael M.
Chen, Nathan H.
Chang, Chiung-Wen
Djoko, Karrera Y.
McEwan, Alastair G.
Kobe, Bostjan
Title Structural basis of thiol-based regulation of formaldehyde detoxification in H. influenzae by a MerR regulator with no sensor region
Formatted title
Structural basis of thiol-based regulation of formaldehyde detoxification in H. influenzae by a MerR regulator with no sensor region
Journal name Nucleic Acids Research   Check publisher's open access policy
ISSN 1362-4962
0305-1048
Publication date 2016-06-15
Year available 2016
Sub-type Article (original research)
DOI 10.1093/nar/gkw543
Open Access Status DOI
Volume 44
Issue 14
Start page 6981
End page 6993
Total pages 13
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2017
Language eng
Formatted abstract
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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
 
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Created: Tue, 28 Jun 2016, 13:45:08 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences