Reading and Writing the Ubiquitin Code Using Genetic Code Expansion

Rishi S Patel; Nipuni M Pannala; Chittaranjan Das

doi:10.1002/cbic.202400190

Reading and Writing the Ubiquitin Code Using Genetic Code Expansion

Chembiochem. 2024 Apr 8:e202400190. doi: 10.1002/cbic.202400190. Online ahead of print.

Authors

Rishi S Patel¹, Nipuni M Pannala¹, Chittaranjan Das²

Affiliations

¹ Purdue University, Chemistry, 560 Oval Dr., 47907, West Lafayette, UNITED STATES.
² Purdue University, Chemistry, 560 Oval Drive, 47907, West Lafayette, UNITED STATES.

PMID: 38588469
DOI: 10.1002/cbic.202400190

Abstract

Deciphering ubiquitin proteoform signaling and its role in disease has been a long-standing challenge in the field. The effects of ubiquitin modifications, its relation to ubiquitin-related machineries, and its signaling output has been particularly limited by its reconstitution and means of characterization. Advances in genetic code expansion have contributed towards addressing these challenges by precision incorporation of unnatural amino acids through site selective codon suppression. This review discusses recent advances in studying the 'writers', 'readers', and 'erasers' of the ubiquitin code using genetic code expansion. Highlighting strategies towards genetically encoded protein ubiquitination, ubiquitin phosphorylation, acylation, and finally surveying ubiquitin interactions, we strive to bring attention to this unique approach towards addressing a widespread proteoform problem.

Keywords: genetic code expansion; post-translational modifications; proteoform; ubiquitin.