CdiA from Enterobacter cloacae delivers a toxic ribosomal RNase into target bacteria

Christina M Beck; Robert P Morse; David A Cunningham; Angelina Iniguez; David A Low; Celia W Goulding; Christopher S Hayes

doi:10.1016/j.str.2014.02.012

CdiA from Enterobacter cloacae delivers a toxic ribosomal RNase into target bacteria

Structure. 2014 May 6;22(5):707-18. doi: 10.1016/j.str.2014.02.012. Epub 2014 Mar 20.

Authors

Christina M Beck¹, Robert P Morse², David A Cunningham¹, Angelina Iniguez², David A Low³, Celia W Goulding⁴, Christopher S Hayes⁵

Affiliations

¹ Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106-9625, USA.
² Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA.
³ 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.
⁴ 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.
⁵ 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.

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.

Publication types

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

MeSH terms

Bacterial Proteins
Bacterial Toxins / chemistry*
Bacterial Toxins / genetics
Bacterial Toxins / metabolism*
Binding Sites
Colicins / chemistry
Contact Inhibition
Crystallography, X-Ray
Enterobacter cloacae / chemistry*
Enterobacter cloacae / genetics
Escherichia coli / growth & development
Models, Molecular
Mutation
Protein Conformation
Protein Structure, Tertiary
RNA, Ribosomal, 16S / metabolism
Ribonucleases / chemistry
Ribonucleases / metabolism
Structural Homology, Protein

Substances

Bacterial Proteins
Bacterial Toxins
Colicins
RNA, Ribosomal, 16S
Ribonucleases

Associated data

PDB/4NTQ

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding