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Mechanistic studies of ribosome‐dependent toxins active during the stringent response (566.8)
Author(s) -
Dunham Christine,
Schureck Marc,
Maehigashi Tatsuya,
Ruangprasert Ajchareeya,
Dunkle Jack,
Miles Stacey
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.566.8
Subject(s) - ribosome , translation (biology) , protein biosynthesis , ribosomal rna , toxin , messenger rna , ribosomal binding site , translational regulation , microbiology and biotechnology , biology , chemistry , computational biology , biochemistry , rna , gene
Regulation of protein synthesis is one mechanism by which bacteria alter their metabolic rates during times of stress. This process is known as the ‘stringent response’ where the presence of deacylated tRNAs bound to the ribosome is one signal that initiates a cascade of events ultimately resulting in the activation of toxin proteins. Type II toxin proteins halt translation by targeting mRNA bound to the ribosome for degradation in a codon‐dependent manner. Here, we present structural studies of different toxin proteins bound to target mRNAs on the 70S ribosome. Our structures reveal novel interactions between conserved toxin residues with the mRNA backbone in the ribosomal A site that helps to rationalize codon specificity by different toxins. Biochemical and in vivo growth assays complement our structural studies to provide a unified mechanism of toxin‐mediated mRNA degradation. Grant Funding Source : Supported by NSF MCB 0953714 and Pew Scholars Program in the Biomedical Sciences