Comparative Proteomics Identifies the Cell-Associated Lethality of M. tuberculosis RelBE-like Toxin-Antitoxin Complexes
| Autor: | William R. Jacobs, Tung Phan, Janet Chiang, Paras Jain, Irina Chernishof, David Eisenberg, Michelle E. Maxson, Linda Miallau, Sum Chan, Christine J. Ahn, Mark A. Arbing, Duilio Cascio |
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| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular Proteomics Protein Conformation Bacterial Toxins Molecular Sequence Data Mycobacterium smegmatis Sequence alignment Biology Crystallography X-Ray medicine.disease_cause Article Catalysis Microbiology Mycobacterium tuberculosis Protein structure Species Specificity Structural Biology medicine Cluster Analysis Amino Acid Sequence Cell Shape Molecular Biology Escherichia coli Peptide sequence Phylogeny biology.organism_classification Multiprotein Complexes Antitoxins Antitoxin Sequence Alignment |
| Zdroj: | Structure. 21:627-637 |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/j.str.2013.02.008 |
| Popis: | SummaryThe 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. |
| Databáze: | OpenAIRE |
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