Pulkit Gupta, Bo Liu, Dorota Klepacki, Vrinda Gupta, Klaus Schulten,
Alexander S. Mankin, and Nora Vazquez-Laslop.
Nascent peptide assists the ribosome in recognizing chemically
distinct small molecules.
Nature Chemical Biology, pp. (6 pages), 2015.
PMID: 26727240.
GUPT2015
Regulation of gene expression in response to the changing environment is critical for cell
survival. For instance, binding of macrolide antibiotics to the ribosome promotes
translation arrest at the leader open reading frames ermCL and ermBL,
which is necessary for inducing the antibiotic resistance genes ermC and
ermB. Cladinose-containing macrolides such as erythromycin (ERY), but not
ketolides such as telithromycin (TEL), arrest translation of ermCL, whereas either
ERY or TEL stall ermBL translation. How the ribosome distinguishes between
chemically similar small molecules is unknown. We show that single amino acid changes in
the leader peptide switch the specificity of recognition of distinct molecules, triggering
gene activation in response to ERY alone, to TEL alone or to both antibiotics or preventing
stalling altogether. Thus, the ribosomal response to chemical signals can be modulated by
minute changes in the nascent peptide, suggesting that protein sequences could have been
optimized for rendering translation sensitive to environmental cues.
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