Prevention of amyloid-like aggregation as a driving force of protein evolution

• Published in: EMBO reports 2007-08, Vol.8 (8), p.737-742
• Main Authors: Monsellier, Elodie, Chiti, Fabrizio
• Format: Article
• Language: English
• Subjects: Aggregates; Amyloid - chemistry; Amyloid - metabolism; Biochemistry; Biochemistry, Molecular Biology; Biophysics; Cellular biology; cross-β; EMBO24; EMBO31; Evolution, Molecular; evolutionary pressure; Glycine - chemistry; Humans; Hydrophobic and Hydrophilic Interactions; Life Sciences; misfolding; Molecular biology; natural selection; negative design; Pathology; Peptides; Proline - chemistry; Protein Folding; Protein Structure, Secondary; Proteins; Proteins - chemistry; Proteins - metabolism; Quality control; Review; Solubility
• ISSN: 1469-221X; 1469-3178; 1469-221X
• DOI: 10.1038/sj.embor.7401034

Uncontrolled protein aggregation is a constant challenge in all compartments of living organisms. The failure of a peptide or protein to remain soluble often results in pathology. So far, more than 40 human diseases have been associated with the formation of extracellular fibrillar aggregates—known as amyloid fibrils—or structurally related intracellular deposits. It is well known that molecular chaperones and elaborate quality control mechanisms exist in the cell to counteract aggregation. However, an increasing number of reports during the past few years indicate that proteins have also evolved structural and sequence‐based strategies to prevent aggregation. This review describes these strategies and the selection pressures that exist on protein sequences to combat their uncontrolled aggregation. We will describe the different types of mechanism evolved by proteins that adopt different conformational states including normally folded proteins, intrinsically disordered polypeptide chains, elastomeric systems and multimodular proteins.