title: The structure of a contact-dependent growth-inhibition (CDI) immunity protein from Neisseria meningitidis MC58.
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.
authors.affiliation: Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne, IL 60439, USA.
authors.forename: Kemin
authors.initials: K
authors.lastname: Tan
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA 92697, USA.
authors.forename: Parker M
authors.initials: PM
authors.lastname: Johnson
authors.affiliation: Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne, IL 60439, USA.
authors.forename: Lucy
authors.initials: L
authors.lastname: Stols
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA 92697, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Boubion
authors.affiliation: Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne, IL 60439, USA.
authors.forename: William
authors.initials: W
authors.lastname: Eschenfeldt
authors.affiliation: Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne, IL 60439, USA.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Babnigg
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA 93106, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Hayes
authors.affiliation: Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne, IL 60439, USA.
authors.forename: Andrezj
authors.initials: A
authors.lastname: Joachimiak
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA 92697, USA.
authors.forename: Celia W
authors.initials: CW
authors.lastname: Goulding
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D000898:Antibiosis / Q000276:immunology; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000276:immunology; D003260:Contact Inhibition / Q000276:immunology; D018360:Crystallography, X-Ray; D004722:Endoribonucleases / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D029867:Xenopus Proteins / Q000737:chemistry; D014982:Xenopus laevis / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; C554743:CdiI protein, E coli; D029968:Escherichia coli Proteins; D011994:Recombinant Proteins; D029867:Xenopus Proteins; D004722:Endoribonucleases; C475059:ENDOU protein, Xenopus
keywords: CdiA-CT toxin domain; CdiI immunity protein; Neisseria meningitidis; contact-dependent growth inhibition; docking studies; toxin–immunity protein complex