Protein Encapsulation in vivo via Transient Disulfide Bond Formation

Abstract

Protein encapsulation complexes play important roles in biology and bionanotechnology. Herein we show that an engineered lumazine synthase nanocage can encapsulate a guest protein via disulfide bonds that transiently link the guest to the inner surface of the nascent nanocage during assembly in bacteria. Engineering the C-terminus of the guest, by adding either another Cys residue or a peptide tag that provides non-covalent affinity, further increased the encapsulation yield. The ability of disulfide bonds to promote protein encapsulation is surprising given the reducing environment inside cells. Nevertheless, disulfide capture represents a simple and novel strategy for protein compartmentalization in vivo.