Protein Aggregation and Its Prediction

The presence of protein aggregates in tissues is the hallmark of more than 40 different human disorders, from neurodegenerative diseases to systemic and localized amyloidosis. On the other hand recombinant protein production is an essential tool for the biotechnology industry and supports expanding areas of basic and biomedical research, including structural genomics and proteomics. However, many recombinant polypeptides, specially those of human origin, undergo irregular or incomplete folding processes, when produced in heterologous hosts, that usually result in their accumulation as insoluble aggregates which are known as inclusion bodies, and resemble those formed in conformational disorders. Consequently, many biologically relevant protein-based drugs are excluded from the market simply because they cannot be harvested in their native form at economically convenient yields. As discussed herein, the biomedical and biotechnological relevance of these two different, but mechanistically related, problems has pushed the study of protein aggregation to evolve from a barely neglected area of protein chemistry to a highly dynamic research field nowadays.