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

Research output: Contribution to journalArticle

13 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

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    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