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Title: Functional plasticity of antibacterial EndoU toxins

Journal Article · · Molecular Microbiology
DOI:https://doi.org/10.1111/mmi.14007· OSTI ID:1491848
 [1];  [2];  [2];  [1];  [1];  [2];  [2];  [3];  [2];  [4];  [5];  [2]
  1. Argonne National Lab. (ANL), Argonne, IL (United States)
  2. Univ. of California, Santa Barbara, CA (United States)
  3. Uppsala Univ., Uppsala (Sweden)
  4. Univ. of California, Irvine, CA (United States)
  5. Argonne National Lab. (ANL), Argonne, IL (United States); Univ. of Chicago, Chicago, IL (United States)

Abstract Bacteria use several different secretion systems to deliver toxic EndoU ribonucleases into neighboring cells. Here, we present the first structure of a prokaryotic EndoU toxin in complex with its cognate immunity protein. The contact‐dependent growth inhibition toxin CdiA‐CT STECO31 from Escherichia coli STEC_O31 adopts the eukaryotic EndoU fold and shares greatest structural homology with the nuclease domain of coronavirus Nsp15. The toxin contains a canonical His‐His‐Lys catalytic triad in the same arrangement as eukaryotic EndoU domains, but lacks the uridylate‐specific ribonuclease activity that characterizes the superfamily. Comparative sequence analysis indicates that bacterial EndoU domains segregate into at least three major clades based on structural variations in the N‐terminal subdomain. Representative EndoU nucleases from clades I and II degrade tRNA molecules with little specificity. In contrast, CdiA‐CT STECO31 and other clade III toxins are specific anticodon nucleases that cleave tRNA Glu between nucleotides C37 and m 2 A38. These findings suggest that the EndoU fold is a versatile scaffold for the evolution of novel substrate specificities. Such functional plasticity may account for the widespread use of EndoU effectors by diverse inter‐bacterial toxin delivery systems.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1491848
Alternate ID(s):
OSTI ID: 1464280
Journal Information:
Molecular Microbiology, Vol. 109, Issue 4; ISSN 0950-382X
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 21 works
Citation information provided by
Web of Science

References (84)

A Family of LIC Vectors for High-Throughput Cloning and Purification of Proteins book January 2009
The active site and mechanism of action of bovine pancreatic ribonuclease. 7. The catalytic mechanism journal October 1962
MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes journal July 2004
New LIC vectors for production of proteins from genes containing rare codons journal September 2013
Unique and Conserved Features of Genome and Proteome of SARS-coronavirus, an Early Split-off From the Coronavirus Group 2 Lineage journal August 2003
Ribosomally encoded antibacterial proteins and peptides from Pseudomonas journal July 2014
CdiA Effectors from Uropathogenic Escherichia coli Use Heterotrimeric Osmoporins as Receptors to Recognize Target Bacteria journal October 2016
The type VII secretion system of Staphylococcus aureus secretes a nuclease toxin that targets competitor bacteria journal October 2016
CdiA from Enterobacter cloacae Delivers a Toxic Ribosomal RNase into Target Bacteria journal May 2014
Refinement of Macromolecular Structures by the Maximum-Likelihood Method journal May 1997
Biochemical and Genetic Analyses of Murine Hepatitis Virus Nsp15 Endoribonuclease journal September 2007
Overview of the CCP 4 suite and current developments journal March 2011
Biochemical Characterization of Arterivirus Nonstructural Protein 11 Reveals the Nidovirus-Wide Conservation of a Replicative Endoribonuclease journal March 2009
Cleavage of the A Site mRNA Codon during Ribosome Pausing Provides a Mechanism for Translational Quality Control journal October 2003
Dali server: conservation mapping in 3D journal May 2010
The structure of a contact-dependent growth-inhibition (CDI) immunity protein from Neisseria meningitidis MC58 journal May 2015
Contact-dependent growth inhibition requires the essential outer membrane protein BamA (YaeT) as the receptor and the inner membrane transport protein AcrB journal October 2008
Activation of contact-dependent antibacterial tRNase toxins by translation elongation factors journal February 2017
Contact-dependent growth inhibition toxins exploit multiple independent cell-entry pathways journal August 2015
Engineering Controllable Protein Degradation journal June 2006
Purification, Cloning, and Characterization of XendoU, a Novel Endoribonuclease Involved in Processing of Intron-encoded Small Nucleolar RNAs in Xenopus laevis journal February 2003
Selection of Orphan Rhs Toxin Expression in Evolved Salmonella enterica Serovar Typhimurium journal March 2014
Unraveling the essential role of CysK in CDI toxin activation journal August 2016
Contact-Dependent Inhibition of Growth in Escherichia coli journal August 2005
Structural Biology of the Arterivirus nsp11 Endoribonucleases journal October 2016
Crystal Structure of a Monomeric Form of Severe Acute Respiratory Syndrome Coronavirus Endonuclease nsp15 Suggests a Role for Hexamerization as an Allosteric Switch journal April 2007
Bovine Pancreatic Ribonuclease: Fifty Years of the First Enzymatic Reaction Mechanism journal September 2011
New Antiviral Target Revealed by the Hexameric Structure of Mouse Hepatitis Virus Nonstructural Protein nsp15 journal July 2006
A New Family of Secreted Toxins in Pathogenic Neisseria Species journal January 2015
Genetically distinct pathways guide effector export through the type VI secretion system: Effector export pathways of type VI secretion journal March 2014
Inference of Macromolecular Assemblies from Crystalline State journal September 2007
A statistic for local intensity differences: robustness to anisotropy and pseudo-centering and utility for detecting twinning journal June 2003
UCSF Chimera?A visualization system for exploratory research and analysis journal January 2004
Chaperone function of FkpA, a heat shock prolyl isomerase, in the periplasm of Escherichia coli journal January 2001
In vitro study of processing of the intron-encoded U16 small nucleolar RNA in Xenopus laevis. journal May 1994
Mutational Analysis of the SARS Virus Nsp15 Endoribonuclease: Identification of Residues Affecting Hexamer Formation journal November 2005
Domain exchange at the 3’ end of the gene encoding the fratricide meningococcal two-partner secretion protein A journal January 2013
Can't you hear me knocking: contact-dependent competition and cooperation in bacteria journal April 2017
Contact-dependent killing by Caulobacter crescentus via cell surface-associated, glycine zipper proteins journal March 2017
The calcium-dependent ribonuclease XendoU promotes ER network formation through local RNA degradation journal October 2014
The Buccaneer software for automated model building. 1. Tracing protein chains journal August 2006
Structural and Functional Analyses of the Severe Acute Respiratory Syndrome Coronavirus Endoribonuclease Nsp15 journal November 2007
Colicin Biology journal March 2007
Mechanism of Action of Bovine Pancreatic Ribonuclease journal July 1966
A short history of SHELX journal December 2007
Structure of a novel antibacterial toxin that exploits elongation factor Tu to cleave specific transfer RNAs journal August 2017
HKL -3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes journal July 2006
Type VI secretion system effectors: poisons with a purpose journal January 2014
Functional Characterization of XendoU, the Endoribonuclease Involved in Small Nucleolar RNA Biosynthesis journal March 2005
The Vibrio cholerae type VI secretion system employs diverse effector modules for intraspecific competition journal April 2014
A widespread family of polymorphic contact-dependent toxin delivery systems in bacteria journal November 2010
Coot model-building tools for molecular graphics journal November 2004
Deciphering key features in protein structures with the new ENDscript server journal April 2014
A novel immunity system for bacterial nucleic acid degrading toxins and its recruitment in various eukaryotic and DNA viral systems journal February 2011
Coronavirus nonstructural protein 15 mediates evasion of dsRNA sensors and limits apoptosis in macrophages journal May 2017
A View to a Kill: The Bacterial Type VI Secretion System journal January 2014
Bacterial Quorum-Sensing Network Architectures journal December 2009
The toxin/immunity network of Burkholderia pseudomallei contact-dependent growth inhibition (CDI) systems: Burkholderia pseudomallei CDI systems journal April 2012
Prolyl-tRNA Pro in the A-site of SecM-arrested Ribosomes Inhibits the Recruitment of Transfer-messenger RNA journal September 2006
A Type VI Secretion System of Pseudomonas aeruginosa Targets a Toxin to Bacteria journal January 2010
Polymorphic toxin systems: Comprehensive characterization of trafficking modes, processing, mechanisms of action, immunity and ecology using comparative genomics journal January 2012
Bacterial killing via a type IV secretion system journal March 2015
A novel family of toxin/antitoxin proteins in Bacillus species journal December 2011
CDI Systems Are Stably Maintained by a Cell-Contact Mediated Surveillance Mechanism journal June 2016
Cleavable C-terminal His-tag vectors for structure determination journal March 2010
A broadly distributed toxin family mediates contact-dependent antagonism between gram-positive bacteria journal July 2017
On the treatment of negative intensity observations journal July 1978
Contact-Dependent Growth Inhibition (CDI) and CdiB/CdiA Two-Partner Secretion Proteins journal November 2015
Sibling Rivalry in Myxococcus xanthus Is Mediated by Kin Recognition and a Polyploid Prophage journal January 2016
EssD, a Nuclease Effector of the Staphylococcus aureus ESS Pathway journal October 2016
Type VI secretion requires a dynamic contractile phage tail-like structure journal February 2012
Identification of a target cell permissive factor required for contact-dependent growth inhibition (CDI) journal February 2012
The structure of the endoribonuclease XendoU: From small nucleolar RNA processing to severe acute respiratory syndrome coronavirus replication journal August 2006
The Vibrio cholerae type VI secretion system displays antimicrobial properties journal October 2010
Major genetic marker of nidoviruses encodes a replicative endoribonuclease journal August 2004
Crystal structure and mechanistic determinants of SARS coronavirus nonstructural protein 15 define an endoribonuclease family journal August 2006
Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication journal February 2017
A Novel Mn++-Dependent Ribonuclease That Functions in U16 SnoRNA Processing inX.Laevis. journal April 1997
Identification of Functional Toxin/Immunity Genes Linked to Contact-Dependent Growth Inhibition (CDI) and Rearrangement Hotspot (Rhs) Systems journal August 2011
Rhs proteins from diverse bacteria mediate intercellular competition journal April 2013
A Dimerization-Dependent Mechanism Drives the Endoribonuclease Function of Porcine Reproductive and Respiratory Syndrome Virus nsp11 journal February 2016
The Severe Acute Respiratory Syndrome Coronavirus Nsp15 Protein Is an Endoribonuclease That Prefers Manganese as a Cofactor journal October 2004
Structural basis of toxicity and immunity in contact-dependent growth inhibition (CDI) systems journal December 2012
Recombineering: Genetic Engineering in Bacteria Using Homologous Recombination journal April 2007

Cited By (4)

Target highlights in CASP13: Experimental target structures through the eyes of their authors journal August 2019
Target highlights in CASP13: Experimental target structures through the eyes of their authors text January 2019
Crystal structure of Nsp15 endoribonuclease NendoU from SARS‐CoV ‐2 journal May 2020
Regulation of Nucleotide Metabolism and Germline Proliferation in Response to Nucleotide Imbalance and Genotoxic Stresses by EndoU Nuclease journal February 2020

Figures / Tables (12)


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