title: Higher-Order Structure in Bacterial VapBC Toxin-Antitoxin Complexes.
abstract: Toxin-antitoxin systems are widespread in the bacterial kingdom, including in pathogenic species, where they allow rapid adaptation to changing environmental conditions through selective inhibition of key cellular processes, such as DNA replication or protein translation. Under normal growth conditions, type II toxins are inhibited through tight protein-protein interaction with a cognate antitoxin protein. This toxin-antitoxin complex associates into a higher-order macromolecular structure, typically heterotetrameric or heterooctameric, exposing two DNA binding domains on the antitoxin that allow auto-regulation of transcription by direct binding to promoter DNA. In this chapter, we review our current understanding of the structural characteristics of type II toxin-antitoxin complexes in bacterial cells, with a special emphasis on the staggering variety of higher-order architecture observed among members of the VapBC family. This structural variety is a result of poor conservation at the primary sequence level and likely to have significant and functional implications on the way toxin-antitoxin expression is regulated.
authors.affiliation: Faculty of Health and Medical Sciences, Department of Drug Design and Pharmacology, University of Copenhagen, Jagtvej 162, DK-2100, Copenhagen, Denmark.
authors.forename: Kirstine L
authors.initials: KL
authors.lastname: Bendtsen
authors.affiliation: Centre for Bacterial Stress Response and Persistence, Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10c, 8000, Aarhus C, Denmark. deb@mbg.au.dk.
authors.forename: Ditlev E
authors.initials: DE
authors.lastname: Brodersen
mesh_terms: D000992:Antitoxins / Q000737:chemistry* / Q000378:metabolism*; D001419:Bacteria / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D000992:Antitoxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004268:DNA-Binding Proteins
keywords: DNA-binding protein; RNA-binding protein; Ribonuclease; Toxin-antitoxin; Transcriptional regulation