3oei

Publication Abstract from PubMed

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.

Comparative proteomics identifies the cell-associated lethality of M. tuberculosis RelBE-like toxin-antitoxin complexes.,Miallau L, Jain P, Arbing MA, Cascio D, Phan T, Ahn CJ, Chan S, Chernishof I, Maxson M, Chiang J, Jacobs WR Jr, Eisenberg DS Structure. 2013 Apr 2;21(4):627-37. doi: 10.1016/j.str.2013.02.008. Epub 2013 Mar , 21. PMID:23523424^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.