Naturally occurring aminoacyl-tRNA synthetases editing-domain mutations that cause mistranslation in Mycoplasma parasites

Li Li, Michal T. Boniecki, Jacob D. Jaffe, Brian S. Imai, Peter M. Yau, Zaida A. Luthey-Schulten, Susan A. Martinis

Research output: Contribution to journalArticlepeer-review

Abstract

Mycoplasma parasites escape host immune responses via mechanisms that depend on remarkable phenotypic plasticity. Identification of these mechanisms is of great current interest. The aminoacyl-tRNA synthetases (AARSs) attach amino acids to their cognate tRNAs, but occasionally make errors that substitute closely similar amino acids. AARS editing pathways clear errors to avoid mistranslation during protein synthesis. We show here that AARSs in Mycoplasma parasites have point mutations and deletions in their respective editing domains. The deleterious effect on editing was confirmed with a specific example studied in vitro. In vivo mistranslation was determined by mass spectrometric analysis of proteins produced in the parasite. These mistranslations are uniform cases where the predicted closely similar amino acid replaced the correct one. Thus, natural AARS editing-domain mutations in Mycoplasma parasites cause mistranslation. We raise the possibility that these mutations evolved as a mechanism for antigen diversity to escape host defense systems.

Original languageEnglish (US)
Pages (from-to)9378-9383
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number23
DOIs
StatePublished - Jun 7 2011

Keywords

  • Amino acid editing
  • Fidelity
  • Host-pathogen interactions
  • Quality control
  • Statistical proteins

ASJC Scopus subject areas

  • General

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