Applications of Genetic Code Expansion in Studying Protein Post-translational Modification

Copyright © 2021 Elsevier Ltd. All rights reserved..

Various post-translational modifications can naturally occur on proteins, regulating the activity, subcellular localization, interaction, or stability of the proteins. However, it can be challenging to decipher the biological implication or physiological roles of site-specific modifications due to their dynamic and sub-stoichiometric nature. Genetic code expansion method, relying on an orthogonal aminoacyl-tRNA synthetase/tRNA pair, enables site-specific incorporation of non-canonical amino acids. Here we focus on the application of genetic code expansion to study site-specific protein post-translational modification in vitro and in vivo. After a brief introduction, we discuss possibilities of incorporating non-canonical amino acids containing post-translational modifications or their mimics into target proteins. This approach is applicable for Ser/Thr/Tyr phosphorylation, Tyr sulfation/nitration/hydroxylation, Lys acetylation/acylation, Lys/His mono-methylation, as well as Arg citrullination. The next section describes the use of a precursor non-canonical amino acid followed by chemical and/or enzymatic reactions to afford the desired modification, such as Cys/Lys acylation, ubiquitin and ubiquitin-like modifications, as well as Lys/Gln methylation. We also discuss means for functional regulation of enzymes involving in post-translational modifications through genetically incorporated non-canonical amino acids. Lastly, the limitations and perspectives of genetic code expansion in studying protein post-translational modification are described.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:434

Enthalten in:

Journal of molecular biology - 434(2022), 8 vom: 30. Apr., Seite 167424

Sprache:

Englisch

Beteiligte Personen:

Chen, Jinghao [VerfasserIn]
Tsai, Yu-Hsuan [VerfasserIn]

Links:

Volltext

Themen:

Amino Acids
Amino Acyl-tRNA Synthetases
EC 6.1.1.-
Genetic code expansion
Journal Article
Non-canonical amino acid
Post-translational modification
Review
Ubiquitin
Unnatural amino acid

Anmerkungen:

Date Completed 18.04.2022

Date Revised 31.05.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.jmb.2021.167424

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM335071635