5D8C

Crystal structure of HiNmlR, a MerR family regulator lacking the sensor domain, bound to promoter DNA

Summary for 5D8C

• Entry DOI: 10.2210/pdb5d8c/pdb
• Descriptor: MerR family regulator protein, DNA (5'-D(*CP*TP*TP*AP*GP*AP*GP*TP*TP*CP*AP*CP*TP*CP*TP*AP*AP*G)-3'), DNA (5'-D(*CP*TP*TP*AP*GP*AP*GP*TP*GP*AP*AP*CP*TP*CP*TP*AP*AP*G)-3'), ... (4 entities in total)
• Functional Keywords: transcription factor, merr, thiol-based genetic switch, dna untwisting, transcription-dna complex, transcription/dna
• Biological source: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd); More
• Total number of polymer chains: 4
• Total formula weight: 42404.27

Authors

Counago, R.M.,Chang, C.W.,Chen, N.H.,Djoko, K.Y.,McEwan, A.G.,Kobe, B. (deposition date: 2015-08-17, release date: 2016-06-29, Last modification date: 2023-09-27)

Primary citation

Counago, R.M.,Chen, N.H.,Chang, C.W.,Djoko, K.Y.,McEwan, A.G.,Kobe, B.
Structural basis of thiol-based regulation of formaldehyde detoxification in H. influenzae by a MerR regulator with no sensor region.
Nucleic Acids Res., 44:6981-6993, 2016

PubMed 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.

PubMed: 27307602
DOI: 10.1093/nar/gkw543

Experimental method

X-RAY DIFFRACTION (2.25 Å)