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Lipid II-independent trans editing of mischarged tRNAs by the penicillin resistance factor MurM

Jennifer Shepherd1, Michael Ibba2

  • 1From the Department of Microbiology and.

The Journal of Biological Chemistry
|July 23, 2013
PubMed

Insights

Streptococcus pneumoniae MurM protein, essential for penicillin resistance, acts as a translation quality control factor. It deacylates mischarged tRNAs, substituting for absent editing proteins and ensuring accuracy in bacterial protein synthesis.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • * *Streptococcus pneumoniae* causes serious nosocomial infections like pneumonia and meningitis.
  • * Penicillin resistance in *S. pneumoniae* is partly due to MurM, an enzyme involved in peptidoglycan synthesis.
  • * The precise role of MurM and its substrates in bacterial physiology, particularly in translation quality control, remains unclear.

Purpose of the Study:

  • * To investigate the substrates provided to MurM by the translation machinery.
  • * To elucidate the function of alanyl-tRNA synthetase (AlaRS) in *S. pneumoniae*.
  • * To determine the role of MurM in translation quality control and its conservation in *S. pneumoniae*.

Main Methods:

  • * Investigated mischarging activities of alanyl-tRNA synthetase (AlaRS) with various tRNAs.
  • * Analyzed the structure of *S. pneumoniae* tRNA(Phe) and its interaction with phenylalanyl-tRNA synthetase (PheRS).
  • * Assessed the lipid-independent trans-editing activity of MurM on deacylating tRNA.

Main Results:

  • * AlaRS mischarged serine and glycine to tRNA(Ala) and alanine, serine, and glycine to tRNA(Phe).
  • * *S. pneumoniae* tRNA(Phe) possesses a unique structural feature preventing editing by PheRS, leading to misaminoacylated tRNA accumulation.
  • * MurM functions as a broad-specificity, lipid-independent trans-editing factor, deacylating tRNA without needing Lipid II.
  • * MurM's editing activity can substitute for the absent AlaXPs proteins, crucial editing homologues found in other bacteria.

Conclusions:

  • * MurM plays a critical role in translation quality control in *S. pneumoniae* by editing mischarged tRNAs.
  • * This editing function is essential for maintaining cellular accuracy, especially given the unique tRNA structure and absence of canonical editing proteins.
  • * MurM's dual role in cell wall synthesis and translation quality control explains its functional conservation in *S. pneumoniae*.
Keywords:
Aminoacyl-tRNA SynthesisAminoacyl-tRNA SynthetasePeptidoglycanTransfer RNA (tRNA)Translation

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