5AH5

Crystal structure of the ternary complex of Agrobacterium radiobacter K84 agnB2 LeuRS-tRNA-LeuAMS

Summary for 5AH5

• Entry DOI: 10.2210/pdb5ah5/pdb
• Related: 5AGH 5AGI 5AGJ
• Descriptor: LEUCINE--TRNA LIGASE, TRNA-LEU TAA ISOACCEPTOR, ZINC ION, ... (7 entities in total)
• Functional Keywords: ligase-rna complex, leucine-trna, leucine-trna ligase activity atp + l-leucine + trna(leu) gives amp + diphosphate + l-leucyl-trna(leu), aminoacyl- trna editing activity, aminoacyl-trna synthetase, protein biosynthesis, toxic moeity 84 resistance, ligase/rna
• Biological source: AGROBACTERIUM RADIOBACTER K84; More
• Cellular location: Cytoplasm : B9JQP8
• Total number of polymer chains: 4
• Total formula weight: 240261.20

Authors

Palencia, A.,Chopra, S.,Virus, C.,Schulwitz, S.,Temple, B.R.,Cusack, S.,Reader, J.S. (deposition date: 2015-02-05, release date: 2016-02-17, Last modification date: 2024-01-10)

Primary citation

Chopra, S.,Palencia, A.,Virus, C.,Schulwitz, S.,Temple, B.R.,Cusack, S.,Reader, J.
Structural Characterization of Antibiotic Self-Immunity tRNA Synthetase in Plant Tumour Biocontrol Agent.
Nat.Commun., 7:12928-, 2016

PubMed Abstract: Antibiotic-producing microbes evolved self-resistance mechanisms to avoid suicide. The biocontrol Agrobacterium radiobacter K84 secretes the Trojan Horse antibiotic agrocin 84 that is selectively transported into the plant pathogen A. tumefaciens and processed into the toxin TM84. We previously showed that TM84 employs a unique tRNA-dependent mechanism to inhibit leucyl-tRNA synthetase (LeuRS), while the TM84-producer prevents self-poisoning by expressing a resistant LeuRS AgnB2. We now identify a mechanism by which the antibiotic-producing microbe resists its own toxin. Using a combination of structural, biochemical and biophysical approaches, we show that AgnB2 evolved structural changes so as to resist the antibiotic by eliminating the tRNA-dependence of TM84 binding. Mutagenesis of key resistance determinants results in mutants adopting an antibiotic-sensitive phenotype. This study illuminates the evolution of resistance in self-immunity genes and provides mechanistic insights into a fascinating tRNA-dependent antibiotic with applications for the development of anti-infectives and the prevention of biocontrol emasculation.

PubMed: 27713402
DOI: 10.1038/NCOMMS12928

Experimental method

X-RAY DIFFRACTION (2.1 Å)