5J4A

CdiA-CT toxin from Burkholderia pseudomallei E479 in complex with cognate CdiI immunity protein

Summary for 5J4A

• Entry DOI: 10.2210/pdb5j4a/pdb
• Related: 5J43 5J5V
• Descriptor: tRNA nuclease CdiA, Immunity protein CdiI (3 entities in total)
• Functional Keywords: complex, toxin, endonuclease, immunity protein
• Biological source: Burkholderia pseudomallei; More
• Cellular location: Target cell, target cell cytoplasm : H9T8G6
• Total number of polymer chains: 4
• Total formula weight: 60758.13

Authors

Goulding, C.W.,Johnson, P.M. (deposition date: 2016-03-31, release date: 2016-07-27, Last modification date: 2024-03-06)

Primary citation

Johnson, P.M.,Gucinski, G.C.,Garza-Sanchez, F.,Wong, T.,Hung, L.W.,Hayes, C.S.,Goulding, C.W.
Functional Diversity of Cytotoxic tRNase/Immunity Protein Complexes from Burkholderia pseudomallei.
J.Biol.Chem., 291:19387-19400, 2016

PubMed Abstract: Contact-dependent growth inhibition (CDI) is a widespread mechanism of inter-bacterial competition. CDI(+) bacteria deploy large CdiA effector proteins, which carry variable C-terminal toxin domains (CdiA-CT). CDI(+) cells also produce CdiI immunity proteins that specifically neutralize cognate CdiA-CT toxins to prevent auto-inhibition. Here, we present the crystal structure of the CdiA-CT/CdiI(E479) toxin/immunity protein complex from Burkholderia pseudomallei isolate E479. The CdiA-CT(E479) tRNase domain contains a core α/β-fold that is characteristic of PD(D/E)XK superfamily nucleases. Unexpectedly, the closest structural homolog of CdiA-CT(E479) is another CDI toxin domain from B. pseudomallei 1026b. Although unrelated in sequence, the two B. pseudomallei nuclease domains share similar folds and active-site architectures. By contrast, the CdiI(E479) and CdiI(1026b) immunity proteins share no significant sequence or structural homology. CdiA-CT(E479) and CdiA-CT(1026b) are both tRNases; however, each nuclease cleaves tRNA at a distinct position. We used a molecular docking approach to model each toxin bound to tRNA substrate. The resulting models fit into electron density envelopes generated by small-angle x-ray scattering analysis of catalytically inactive toxin domains bound stably to tRNA. CdiA-CT(E479) is the third CDI toxin found to have structural homology to the PD(D/E)XK superfamily. We propose that CDI systems exploit the inherent sequence variability and active-site plasticity of PD(D/E)XK nucleases to generate toxin diversity. These findings raise the possibility that many other uncharacterized CDI toxins may belong to the PD(D/E)XK superfamily.

PubMed: 27445337
DOI: 10.1074/jbc.M116.736074

Experimental method

X-RAY DIFFRACTION (2.004 Å)