The structure of a contact-dependent growth-inhibition (CDI) immunity protein from Neisseria meningitidis MC58

Acta Crystallogr F Struct Biol Commun. 2015 Jun;71(Pt 6):702-9. doi: 10.1107/S2053230X15006585. Epub 2015 May 20.

Abstract

Contact-dependent growth inhibition (CDI) is an important mechanism of intercellular competition between neighboring Gram-negative bacteria. CDI systems encode large surface-exposed CdiA effector proteins that carry a variety of C-terminal toxin domains (CdiA-CTs). All CDI(+) bacteria also produce CdiI immunity proteins that specifically bind to the cognate CdiA-CT and neutralize its toxin activity to prevent auto-inhibition. Here, the X-ray crystal structure of a CdiI immunity protein from Neisseria meningitidis MC58 is presented at 1.45 Å resolution. The CdiI protein has structural homology to the Whirly family of RNA-binding proteins, but appears to lack the characteristic nucleic acid-binding motif of this family. Sequence homology suggests that the cognate CdiA-CT is related to the eukaryotic EndoU family of RNA-processing enzymes. A homology model is presented of the CdiA-CT based on the structure of the XendoU nuclease from Xenopus laevis. Molecular-docking simulations predict that the CdiA-CT toxin active site is occluded upon binding to the CdiI immunity protein. Together, these observations suggest that the immunity protein neutralizes toxin activity by preventing access to RNA substrates.

Keywords: CdiA-CT toxin domain; CdiI immunity protein; Neisseria meningitidis; contact-dependent growth inhibition; docking studies; toxin–immunity protein complex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Antibiosis / immunology
  • Bacterial Toxins / antagonists & inhibitors*
  • Bacterial Toxins / chemistry*
  • Bacterial Toxins / immunology
  • Contact Inhibition / immunology
  • Crystallography, X-Ray
  • Endoribonucleases / chemistry
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / immunology
  • Gene Expression
  • Molecular Docking Simulation
  • Molecular Sequence Data
  • Neisseria meningitidis / chemistry*
  • Neisseria meningitidis / immunology
  • Neisseria meningitidis / metabolism
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Sequence Alignment
  • Structural Homology, Protein
  • Xenopus Proteins / chemistry
  • Xenopus laevis / metabolism

Substances

  • Bacterial Toxins
  • CdiI protein, E coli
  • Escherichia coli Proteins
  • Recombinant Proteins
  • Xenopus Proteins
  • Endoribonucleases
  • ENDOU protein, Xenopus

Associated data

  • PDB/4Q7O