Comparative proteomics identifies the cell-associated lethality of M. tuberculosis RelBE-like toxin-antitoxin complexes

Linda Miallau, Paras Jain, Mark A. Arbing, Duilio Cascio, Tung Phan, Christine J. Ahn, Sum Chan, Irina Chernishof, Michelle Maxson, Janet Chiang, William R. Jacobs, David S. Eisenberg

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12 Scopus citations

Abstract

The Mycobacterium tuberculosis (Mtb) genome encodes approximately 90 toxin-antitoxin protein complexes, including three RelBE family members, which are believed to play a major role in bacterial fitness and pathogenicity. We have determined the crystal structures of Mtb RelBE-2 and RelBE-3, and the structures reveal homologous heterotetramers. Our structures suggest RelE-2, and by extension the closely related RelE-1, use a different catalytic mechanism than RelE-3, because our analysis of the RelE-2 structure predicts additional amino acid residues that are likely to be functionally significant and are missing from analogous positions in the RelE-3 structure. Toxicity assays corroborate our structural findings; overexpression of RelE-3, whose active site is more similar to Escherichia coli YoeB, has limited consequences on bacterial growth, whereas RelE-1 and RelE-2 overexpression results in acute toxicity. Moreover, RelE-2 overexpression results in an elongated cell phenotype in Mycobacterium smegmatis and protects M. tuberculosis against antibiotics, suggesting a different functional role for RelE-2.

Original languageEnglish (US)
Pages (from-to)627-637
Number of pages11
JournalStructure
Volume21
Issue number4
DOIs
StatePublished - Apr 2 2013

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ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Miallau, L., Jain, P., Arbing, M. A., Cascio, D., Phan, T., Ahn, C. J., Chan, S., Chernishof, I., Maxson, M., Chiang, J., Jacobs, W. R., & Eisenberg, D. S. (2013). Comparative proteomics identifies the cell-associated lethality of M. tuberculosis RelBE-like toxin-antitoxin complexes. Structure, 21(4), 627-637. https://doi.org/10.1016/j.str.2013.02.008