Mechanisms of Toxin Inhibition and Transcriptional Repression by Escherichia coli DinJ-YafQ

• Type of Material: Article
• Authors: Ajchareeya Ruangprasert, Emory University; Tatsuya Maehigashi, Emory University; Stacey J. Miles, Emory University; Nisha Giridharan, Emory University; Julie X. Liu, Emory University; Christine Dunham, Emory University
• Language: English
• Date: 2014-07-25
• Publisher: American Society for Biochemistry and Molecular Biology
• Publication Version: Final Published Version
• Copyright Statement: © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1074/jbc.M114.573006
• Title of Journal or Parent Work: Journal of Biological Chemistry
• ISSN: 0021-9258
• Volume: 289
• Issue: 30
• Start Page: 20559
• End Page: 20569
• Grant/Funding Information: This work was supported by National Science Foundation CAREER Award MCB 0953714 (to C. M. D.).
• Keywords: STRUCTURAL BASIS; YEFM-YOEB; COMPLEX; CONDITIONAL COOPERATIVITY; CRYSTAL-STRUCTURE; PERSISTER CELLS; Life Sciences & Biomedicine; ANTITOXIN SYSTEM; Biochemistry & Molecular Biology; LON PROTEASE; Science & Technology; GENERAL STRESS-RESPONSE; YOEB TOXIN
• Research Categories: Chemistry, Biochemistry

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.