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Type: Artigo
Title: Structural Basis Of Thiol-based Regulation Of Formaldehyde Detoxification In H. Influenzae By A Merr Regulator With No Sensor Region
Author: Counago
Rafael M.; Chen
Nathan H.; Chang
Chiung-Wen; Djoko
Karrera Y.; McEwan
Alastair G.; Kobe
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.
Subject: Crystal-structure;transcriptional Activation
Haemophilus-influenzae;nitrosative Stress;escherichia-coli;dna;family;system;mechanism;gene
Editor: Oxford Univ Press
Rights: aberto
Identifier DOI: 10.1093/nar/gkw543
Date Issue: 2016
Appears in Collections:Unicamp - Artigos e Outros Documentos

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