Co-evolution of quaternary organization and novel RNA tertiary interactions revealed in the crystal structure of a bacterial protein-RNA toxin-antitoxin system

Nucleic Acids Research
Feng RaoGeorge P C Salmond

Abstract

Genes encoding toxin-antitoxin (TA) systems are near ubiquitous in bacterial genomes and they play key roles in important aspects of bacterial physiology, including genomic stability, formation of persister cells under antibiotic stress, and resistance to phage infection. The CptIN locus from Eubacterium rectale is a member of the recently-discovered Type III class of TA systems, defined by a protein toxin suppressed by direct interaction with a structured RNA antitoxin. Here, we present the crystal structure of the CptIN protein-RNA complex to 2.2 Å resolution. The structure reveals a new heterotetrameric quaternary organization for the Type III TA class, and the RNA antitoxin bears a novel structural feature of an extended A-twist motif within the pseudoknot fold. The retention of a conserved ribonuclease active site as well as traits normally associated with TA systems, such as plasmid maintenance, implicates a wider functional role for Type III TA systems. We present evidence for the co-variation of the Type III component pair, highlighting a distinctive evolutionary process in which an enzyme and its substrate co-evolve.

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Citations

Mar 19, 2016·Nature Chemical Biology·Rebecca Page, Wolfgang Peti
Jun 21, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Barbara Kędzierska, Finbarr Hayes
Oct 1, 2016·Toxins·Nathalie GoedersGeorge P C Salmond
May 25, 2016·Experimental Biology and Medicine·Nathan P Coussens, Dayle A Daines
Aug 8, 2019·The Journal of Trauma and Acute Care Surgery·Zi-Sen ZhangLiang-Ming Liu
Jan 8, 2020·Toxins·José Antonio AgüeroLaurent Falquet
Oct 9, 2018·Wiley Interdisciplinary Reviews. RNA·Lauren R Walling, J Scott Butler
Nov 15, 2018·International Journal of Molecular Sciences·Guodong HuJihua Wang
Apr 27, 2021·Frontiers in Molecular Biosciences·Milan GerovacAlexandre Smirnov

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Methods Mentioned

BETA
PCR
X-ray
size exclusion chromatography
gel filtration

Software Mentioned

REFMAC5
iMOSFLM
TRUNCATE
AutoSolve
AMIGOS
PHENIX
SCALA
CCP4
BUCCANEER
CptN

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