Applications of genetic code expansion in the study of lysine acylation
10.11665/j.issn.1000-5048.2023041401
- VernacularTitle:遗传密码子拓展技术在赖氨酸酰化修饰研究中的应用
- Author:
Ying KONG
1
;
Hui YE
;
Chang SHAO
;
Haiping HAO
Author Information
1. 中国药科大学药物代谢动力学重点实验室
- Publication Type:Journal Article
- Keywords:
unnatural amino acids;
lysine acylation;
genetic code expansion;
proteomics
- From:
Journal of China Pharmaceutical University
2023;54(5):519-526
- CountryChina
- Language:Chinese
-
Abstract:
Lysine acylation is a ubiquitous protein modification that controls various aspects of protein function. However, it can be challenging to decipher the biological function of site-specific acylation modifications in living cells.The recently developed genetic code expansion (GCE) technology has enabled site-specific incorporation of unnatural amino acids (UAAs) that are structurally consistent with the natural acylation modifications in vivo through orthogonal aminoacyl-tRNA synthetase/tRNA pairs, thus facilitating the study of physicochemical properties and biological behaviors of homogeneously acylated proteins.Besides, GCE technology allows for the targeted introduction of UAAs that mimic acylation modifications but cannot be recognized by deacylases, which improves the stability of lysine acylation modification products.Moreover, the insertion of photo-crosslinked UAAs at specific sites of the target protein has been used to elucidate the reciprocal proteome of acylated modified proteins.Based on the introduction of different structural and functional acylation modifications, we described the novel design of GCE technology combined with three types of UAAs, and their application in studying the functional effects of protein acylation modifications on the enzyme activity, protein stability, cellular localization, protein-DNA interactions and protein-protein interactions of target proteins, with a description of the limitations and prospects of GCE technology in studying protein acylation modification.
