Coiled-Coil Based Inclusion Bodies and Their Potential Applications

The production of recombinant proteins using microbial cell factories is frequently associated with the formation of inclusion bodies (IBs). These proteinaceous entities can be sometimes a reservoir of stable and active protein, might display good biocompatibility, and are produced efficiently and cost-effectively. Thus, these submicrometric particles are increasingly exploited as functional biomaterials for biotechnological and biomedical purposes. The fusion of aggregation-prone sequences to the target protein is a successful strategy to sequester soluble recombinant polypeptides into IBs. Traditionally, the use of these IB-tags results in the formation of amyloid-like scaffolds where the protein of interest is trapped. This amyloid conformation might compromise the protein's activity and be potentially cytotoxic. One promising alternative to overcome these limitations exploits the coiled-coil fold, composed of two or more alpha-helices and widely used by nature to create supramolecular assemblies. In this review, we summarize the state-of-the-art of functional IBs technology, focusing on the coiled-coil-assembly strategy, describing its advantages and applications, delving into future developments and necessary improvements in the field.

Automated summary

Inclusion bodies are commonly associated with the production of recombinant proteins, serving as reservoirs for stable and active proteins, with potential bio-compatibility for biotechnological and biomedical applications. While the fusion of aggregation-prone sequences can effectively sequester soluble recombinant polypeptides into inclusion bodies, the amyloid-like scaffolds formed may compromise protein activity and be potentially cytotoxic. An alternative strategy using coiled-coil fold provides promising opportunities for creating supramolecular assemblies with advantages and applications in the field.