Self-assembling, protein-based intracellular bacterial organelles: emerging vehicles for encapsulating, targeting and delivering therapeutical cargoes

Abstract

Many bacterial species contain intracellular nano- and micro-compartments consisting of self-assembling proteins that form protein-only shells. These structures are built up by combinations of a reduced number of repeated elements, from 60 repeated copies of one unique structural element self-assembled in encapsulins of 24 nm to 10,000-20,000 copies of a few protein species assembled in a organelle of around 100-150 nm in cross-section. However, this apparent simplicity does not correspond to the structural and functional sophistication of some of these organelles. They package, by not yet definitely solved mechanisms, one or more enzymes involved in specific metabolic pathways, confining such reactions and sequestering or increasing the inner concentration of unstable, toxics or volatile intermediate metabolites. From a biotechnological point of view, we can use the self assembling properties of these particles for directing shell assembling and enzyme packaging, mimicking nature to design new applications in biotechnology. Upon appropriate engineering of the building blocks, they could act as a new family of self-assembled, protein-based vehicles in Nanomedicine to encapsulate, target and deliver therapeutic cargoes to specific cell types and/or tissues. This would provide a new, intriguing platform of microbial origin for drug delivery.

Figure 1

Model for the hierarchical assembly of a typical bacterial microcompartment. The facets of these icosahedral nano-cages are made of one type of protein (in light blue) that further self-assemble to give hexamers. On the other hand, the vertices are formed by pentamers resulting of the self-assembly of a different protein (in orange). Pores allowing traficking of molecules are located at the center of each hexamer and pentamer. Sizes can range from 20-25 nm for the encapsulin shell to 100-150 nm for carboxysomes.

Figure 2

Targeting and encapsulation of proteins into BMCs nano-cages. In some cases (panel A), a stretch of ~15-20 aminoacids (in green) located at the N-terminus of the inner cargo protein (in red) directs and binds it to specific sites on the inner surface of the shell protein (in blue). For other bacterial microcompartments (panel B), the cargo protein (in red) is synthesized together with the shell-forming domain (in blue) from one unique gene.