Systems-level analysis of protein quality in inclusion body-forming Escherichia coli cells

Recombinant proteins produced in Escherichia coli often aggregate as amorphous masses of insoluble material known as inclusion bodies. Being quite homogeneous in their composition, inclusion bodies display amyloid-like properties such as sequence-dependent protein-protein interactions, seeding-driven deposition of their components and β-sheet intermolecular architecture. However, inclusion bodies formed by different proteins and enzymes also show important extents of native-like secondary structure and include significant proportions of properly folded, functional protein, which makes them suitable to be used in catalytic processes. Inclusion bodies are formed as a result of the incapability of the quality control cell system to cope with the non physiological amounts of misfolding-prone proteins produced upon recombinant gene expression. Multiple cellular proteins involved in the quality control, namely chaperones and proteases, participate in their formation and co-ordinately determine the amount of aggregated protein, the size of aggregates and the main structural and functional properties of the embedded polypeptides, such as their inner molecular organization. © 2009 Springer Netherlands.