Protein aggregation occurs in several diseases, including Parkinson's and Alzheimer's diseases but little is known about the molecular basis or specificity of this aggregation. In January 22 online Nature Structural Biology, Fabrizio Chiti from Università degli Studi di Firenze, Italy and collaborators at University of Cambridge, England show that the aggregation and folding can be attributed to the intrinsic conformational preferences of the denatured polypeptide chain.

Chiti et al. studied the effects of 40 single point mutations on the conversion of the denatured form of the α/β protein acylphosphatase (AcP) into insoluble aggregates. They found that all the mutations that significantly perturb the rate of aggregation are located in two specific regions of the protein sequence. The changes in aggregation rate upon mutation correlate with changes in the hydrophobicity and sheet propensity of these regions. In addition, the two regions that determine the aggregation rate are...