Post‐Assembly Modification of Protein Cages by Ubc9‐Mediated Lysine Acylation. (15th September 2022)

• Record Type: Journal Article
• Authors: Levasseur, Mikail D.; Hofmann, Raphael; Edwardson, Thomas G. W.; Hehn, Svenja; Thanaburakorn, Manutsawee; Bode, Jeffrey W.; Hilvert, Donald
• Is Part Of: Chembiochem. Volume 23:Number 20(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-15
• Subjects: enzymes -- LACE -- lumazine synthases -- protein cages -- protein engineering; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202200332
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Although viruses have been successfully repurposed as vaccines, antibiotics, and anticancer therapeutics, they also raise concerns regarding genome integration and immunogenicity. Virus‐like particles and non‐viral protein cages represent a potentially safer alternative but often lack desired functionality. Here, we investigated the utility of a new enzymatic bioconjugation method, called lysine acylation using conjugating enzymes (LACE), to chemoenzymatically modify protein cages. We equipped two structurally distinct protein capsules with a LACE‐reactive peptide tag and demonstrated their modification with diverse ligands. This modular approach combines the advantages of chemical conjugation and genetic fusion and allows for site‐specific modification with recombinant proteins as well as synthetic peptides with facile control of the extent of labeling. This strategy has the potential to fine‐tune protein containers of different shape and size by providing them with new properties that go beyond their biologically native functions. Abstract : Enzyme‐directed post‐assembly modification of protein cages holds promise for the development of new delivery and vaccine platforms. Here, we demonstrate the utility of Ubc9‐mediated lysine acylation using conjugating enzymes (LACE) for the on‐demand decoration of two proteinaceous compartments with small molecules, peptides, and proteins.