2xdb

From Proteopedia

Jump to: navigation, search

A processed non-coding RNA regulates a bacterial antiviral system

Structural highlights

2xdb is a 2 chain structure with sequence from Pectobacterium atrosepticum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.55Å
Ligands:A23, CO, SO4
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TOXN_PECAT Toxic component of a type III toxin-antitoxin (TA) system. An endoribonuclease which is active independently of the ribosome, cleaving between the second and third A of AAA(U/G) sequences, although not all occurrences of this tetranucleotide are cleaved (PubMed:23267117). Digests many mRNA species, including its own transcript and its cognate antitoxin RNA ToxI. ToxI has 5.5 nearly identical 36 nucleotide-long repeats (a single repeat neutralizes the toxin in vivo); a single repeat folds into a pseudoknot which binds the toxin (PubMed:21240270). The ToxI precursor RNA is a preferential target in vivo and is progressively degraded to single repeat lengths as ToxN-ToxI complex self-assembly occurs (PubMed:23267117). In vivo expression of ToxI antitoxin inhibits endonuclease activity of ToxN (PubMed:23267117). The toxin alone inhibits growth when expressed in E.coli without causing cell lysis; this bacteriostatic effect is neutralized by cognate RNA antitoxin ToxI (PubMed:19124776, PubMed:23267117). Non-cognate antitoxin RNA from B.thuringiensis does not inhibit this toxin (PubMed:23267117). The RNA antitoxin is less stable than the proteinaceous toxin; synthesis of ToxI in the absence of new ToxN synthesis restores growth and also detectable accumulation of the ToxN protein (PubMed:19124776). Negatively regulates its own operon in complex with ToxI (PubMed:19633081). The toxin-antitoxin system functions in plasmid maintenance (a plasmid addiction system) (PubMed:23267117).[1] [2] [3] [4] The TA system protects P.atrosepticum strain 1043 against phage phiM1 and phiA2, E.coli against some but not all coliphages and S.marcescens against some bacteriophages, causing an abortive infection (Abi phenotype) (PubMed:19124776). Also protects P.atrosepticum strain 1043 against phage phiTE; phage that escape Abi and grow in this bacterium have evolved a pseudo-ToxI RNA by expanding a pre-existing sequence similar to the bona fide ToxI repeats (PubMed:23109916).[5] [6]

Publication Abstract from PubMed

The >/=10(30) bacteriophages on Earth relentlessly drive adaptive coevolution, forcing the generation of protective mechanisms in their bacterial hosts. One such bacterial phage-resistance system, ToxIN, consists of a protein toxin (ToxN) that is inhibited in vivo by a specific RNA antitoxin (ToxI); however, the mechanisms for this toxicity and inhibition have not been defined. Here we present the crystal structure of the ToxN-ToxI complex from Pectobacterium atrosepticum, determined to 2.75-A resolution. ToxI is a 36-nucleotide noncoding RNA pseudoknot, and three ToxI monomers bind to three ToxN monomers to generate a trimeric ToxN-ToxI complex. Assembly of this complex is mediated entirely through extensive RNA-protein interactions. Furthermore, a 2'-3' cyclic phosphate at the 3' end of ToxI, and catalytic residues, identify ToxN as an endoRNase that processes ToxI from a repetitive precursor but is regulated by its own catalytic product.

A processed noncoding RNA regulates an altruistic bacterial antiviral system.,Blower TR, Pei XY, Short FL, Fineran PC, Humphreys DP, Luisi BF, Salmond GP Nat Struct Mol Biol. 2011 Feb;18(2):185-90. Epub 2011 Jan 16. PMID:21240270[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Loading citation details..
Citations
33 reviews cite this structure
Yamaguchi et al. (2011)
No citations found

References

  1. Fineran PC, Blower TR, Foulds IJ, Humphreys DP, Lilley KS, Salmond GP. The phage abortive infection system, ToxIN, functions as a protein-RNA toxin-antitoxin pair. Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):894-9. Epub 2009 Jan 5. PMID:19124776 doi:10.1073/pnas.0808832106
  2. Blower TR, Fineran PC, Johnson MJ, Toth IK, Humphreys DP, Salmond GP. Mutagenesis and functional characterization of the RNA and protein components of the toxIN abortive infection and toxin-antitoxin locus of Erwinia. J Bacteriol. 2009 Oct;191(19):6029-39. PMID:19633081 doi:10.1128/JB.00720-09
  3. Blower TR, Pei XY, Short FL, Fineran PC, Humphreys DP, Luisi BF, Salmond GP. A processed noncoding RNA regulates an altruistic bacterial antiviral system. Nat Struct Mol Biol. 2011 Feb;18(2):185-90. Epub 2011 Jan 16. PMID:21240270 doi:10.1038/nsmb.1981
  4. Short FL, Pei XY, Blower TR, Ong SL, Fineran PC, Luisi BF, Salmond GP. Selectivity and self-assembly in the control of a bacterial toxin by an antitoxic noncoding RNA pseudoknot. Proc Natl Acad Sci U S A. 2012 Dec 24. PMID:23267117 doi:http://dx.doi.org/10.1073/pnas.1216039110
  5. Fineran PC, Blower TR, Foulds IJ, Humphreys DP, Lilley KS, Salmond GP. The phage abortive infection system, ToxIN, functions as a protein-RNA toxin-antitoxin pair. Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):894-9. Epub 2009 Jan 5. PMID:19124776 doi:10.1073/pnas.0808832106
  6. Blower TR, Evans TJ, Przybilski R, Fineran PC, Salmond GP. Viral evasion of a bacterial suicide system by RNA-based molecular mimicry enables infectious altruism. PLoS Genet. 2012;8(10):e1003023. PMID:23109916 doi:10.1371/journal.pgen.1003023
  7. Blower TR, Pei XY, Short FL, Fineran PC, Humphreys DP, Luisi BF, Salmond GP. A processed noncoding RNA regulates an altruistic bacterial antiviral system. Nat Struct Mol Biol. 2011 Feb;18(2):185-90. Epub 2011 Jan 16. PMID:21240270 doi:10.1038/nsmb.1981

Contents


PDB ID 2xdb

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools