title: CdiA from Enterobacter cloacae delivers a toxic ribosomal RNase into target bacteria.
abstract: Contact-dependent growth inhibition (CDI) is one mechanism of inter-bacterial competition. CDI(+) cells export large CdiA effector proteins, which carry a variety of C-terminal toxin domains (CdiA-CT). CdiA-CT toxins are specifically neutralized by cognate CdiI immunity proteins to protect toxin-producing cells from autoinhibition. Here, we use structure determination to elucidate the activity of a CDI toxin from Enterobacter cloacae (ECL). The structure of CdiA-CT(ECL) resembles the C-terminal nuclease domain of colicin E3, which cleaves 16S ribosomal RNA to disrupt protein synthesis. In accord with this structural homology, we show that CdiA-CT(ECL) uses the same nuclease activity to inhibit bacterial growth. Surprisingly, although colicin E3 and CdiA(ECL) carry equivalent toxin domains, the corresponding immunity proteins are unrelated in sequence, structure, and toxin-binding site. Together, these findings reveal unexpected diversity among 16S rRNases and suggest that these nucleases are robust and versatile payloads for a variety of toxin-delivery platforms.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106-9625, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Beck
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Morse
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106-9625, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Cunningham
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Angelina
authors.initials: A
authors.lastname: Iniguez
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106-9625, USA; Biomolecular Science and Engineering Program, University of California, Santa Barbara, Santa Barbara, CA 93106-9625, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Low
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA; Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Celia W
authors.initials: CW
authors.lastname: Goulding
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106-9625, USA; Biomolecular Science and Engineering Program, University of California, Santa Barbara, Santa Barbara, CA 93106-9625, USA. Electronic address: chayes@lifesci.ucsb.edu.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Hayes
mesh_terms: D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D003087:Colicins / Q000737:chemistry; D003260:Contact Inhibition; D018360:Crystallography, X-Ray; D016972:Enterobacter cloacae / Q000737:chemistry* / Q000235:genetics; D004926:Escherichia coli / Q000254:growth & development; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012336:RNA, Ribosomal, 16S / Q000378:metabolism; D012260:Ribonucleases / Q000737:chemistry / Q000378:metabolism; D040681:Structural Homology, Protein
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003087:Colicins; D012336:RNA, Ribosomal, 16S; D012260:Ribonucleases