Genetic code expansion reveals aminoacylated lysine ubiquitination mediated by UBE2W

ABSTRACT: Protein post-translational modification regulates near every aspect of cellular processes in eukaryotes. However, the identification of new protein post-translational modification is very challenging. Here, using genetically encoded unnatural amino acids as chemical probes, we report the identification and validation of a previously unreported form of protein post-translational modification, aminoacylated lysine ubiquitination, in which the modification occurs on the α-amine group of aminoacylated lysine. We identify more than two thousands of unique aminoacylated lysine ubiquitination sites on all 20 aminoacylated lysines in two human cell lines. The aminoacylated lysine ubiquitination modifications can mediate rapid protein degradation, complementing the canonical lysine ubiquitination-mediated proteome degradation. Furthermore, we demonstrate that the ubiquitin conjugating enzyme UBE2W acts as a writer of aminoacylated lysine ubiquitination and facilitates the ubiquitination of internal α-amine groups on proteins using an unexpected enzymatic activity. More broadly, the discovery and validation of aminoacylated lysine ubiquitination paves the way for the identification and verification of new protein post-translation modifications with the genetic code expansion strategy.

ORGANISM(S): Homo Sapiens

SUBMITTER: Shixian Lin  

PROVIDER: PXD035166 | iProX | Wed Jul 20 00:00:00 BST 2022

REPOSITORIES: iProX