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The Role of Release Factors in the Hydrolysis of Ester Bond in Peptidyl-tRNA

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Abstract

Class I release factors (RFs) recognize stop codons in the sequences of mRNAs and are required for the hydrolysis of peptidyl-tRNA in the ribosomal P site during the final step of protein synthesis in bacteria, resulting in the release of a complete polypeptide chain from the ribosome. A key role in this process belongs to the highly conserved GGQ motif in RFs. Mutations in this motif can reduce the hydrolysis rate or even completely inhibit the reaction. Previously, it was hypothesized that the amino acid residues of GGQ (especially glutamine) are essential for the proper coordination of the water molecule for subsequent hydrolysis of the ester bond. However, available structures of the 70S ribosome termination complex do not allow unambiguous identification of the exact orientation of the carbonyl group in peptidyl-tRNA relative to the GGQ, as well as of the position of the catalytic water molecule in the peptidyl transferase center (PTC). This mini-review summarizes key facts and hypotheses on the role of GGQ in the catalysis of peptide release, as well as suggests and discusses future experiments aimed to produce high-quality structural data for deciphering the precise mechanism of RF-mediated catalysis.

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Abbreviations

PTC:

peptidyl transferase center

RF:

release factor

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Funding

This work was supported by the Illinois State Start-up Funds and by the National Science Foundation (grant no. MCB-1907273).

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Authors and Affiliations

  1. Department of Biological Sciences, College of Liberal Arts and Sciences, University of Illinois at Chicago, 60607, Chicago, Illinois, USA

    Samson M. Balasanyants, Elena V. Aleksandrova & Yury S. Polikanov

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  1. Samson M. Balasanyants
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  2. Elena V. Aleksandrova
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  3. Yury S. Polikanov
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Correspondence to Yury S. Polikanov.

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The authors declare no conflict of interests in financial or any other sphere. This article does not contain a description of studies with human participants or animals performed by any of the authors.

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Balasanyants, S.M., Aleksandrova, E.V. & Polikanov, Y.S. The Role of Release Factors in the Hydrolysis of Ester Bond in Peptidyl-tRNA. Biochemistry Moscow 86, 1122–1127 (2021). https://doi.org/10.1134/S0006297921090078

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