Nature Structural Biology pp 137 - 143

Protein aggregates may be the cause for several human disorders, including Parkinson's and Alzheimer's diseases. However, little is known about the molecular determinants that drive the formation of such aggregates. A study in the February issue of Nature Structural Biology now reveals the principles underlying aggregation for, at least, one small model protein. The findings may provide clues to improved therapeutic approaches.

Chris Dobson at University of Cambridge, England, and collaborators at Universit� degli Studi di Firenze, Italy, have found that, in a small protein called acyl phosphatase, mutations at only a few positions along the polypeptide chain affect the rate of aggregation. Furthermore, the positions are different from those that drive the formation of the native (correct) structure. These results suggest that specific amino acid residues may form intermolecular interactions that nucleate the conversion of polypeptide into aggregates, and that natural proteins may have evolved to avoid forming such interactions in the folding reaction.