title: Mechanisms of toxin inhibition and transcriptional repression by Escherichia coli DinJ-YafQ.
abstract: Bacteria encounter environmental stresses that regulate a gene expression program required for adaptation and survival. Here, we report the 1.8-Å crystal structure of the Escherichia coli toxin-antitoxin complex YafQ-(DinJ)2-YafQ, a key component of the stress response. The antitoxin DinJ dimer adopts a ribbon-helix-helix motif required for transcriptional autorepression, and toxin YafQ contains a microbial RNase fold whose proposed active site is concealed by DinJ binding. Contrary to previous reports, our studies indicate that equivalent levels of transcriptional repression occur by direct interaction of either YafQ-(DinJ)2-YafQ or a DinJ dimer at a single inverted repeat of its recognition sequence that overlaps with the -10 promoter region. Surprisingly, multiple YafQ-(DinJ)2-YafQ complexes binding to the operator region do not appear to amplify the extent of repression. Our results suggest an alternative model for transcriptional autorepression that may be novel to DinJ-YafQ.
authors.affiliation: From the Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322.
authors.forename: Ajchareeya
authors.initials: A
authors.lastname: Ruangprasert
authors.affiliation: From the Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Maehigashi
authors.affiliation: From the Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322.
authors.forename: Stacey J
authors.initials: SJ
authors.lastname: Miles
authors.affiliation: From the Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322.
authors.forename: Nisha
authors.initials: N
authors.lastname: Giridharan
authors.affiliation: From the Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322.
authors.forename: Julie X
authors.initials: JX
authors.lastname: Liu
authors.affiliation: From the Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322 christine.m.dunham@emory.edu.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Dunham
mesh_terms: D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D055503:Protein Multimerization / Q000502:physiology; D020836:Protein Structure, Quaternary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D001427:Bacterial Toxins; C523349:DinJ protein, E coli; D029968:Escherichia coli Proteins; D012097:Repressor Proteins; C523350:YafQ protein, E coli
keywords: Bacterial Toxin; Energy Metabolism; Ribbon-Helix-Helix Factor; Stress Response; Toxin-Antitoxin Complexes; Transcription Repressor; X-ray Crystallography