Assessing the role of aromatic residues in the amyloid aggregation of human muscle acylphosphatase

作者：Bemporad F; Taddei N; Stefani M; Chiti F^*

来源：Protein Science, 2006, 15(4): 862-870.

DOI：10.1110/ps.051915806

• assembly
• aggregation mechanism
• phenylalanine
• molecular recognition
• aromatic-aromatic interaction
• 2,2,2-trifluoroethanol

Among the many parameters that have been proposed to promote amyloid fibril formation is the pi-stacking of aromatic residues. We have studied the amyloid aggregation of several mutants of human muscle acylphosphatase in which an aromatic residue was substituted with a non-aromatic one. The aggregation rate was determined using the Thioflavin T test under conditions in which the variants populated initially an ensemble of partially unfolded conformations. Substitutions in aggregation-promoting fragments of the sequence result in a dramatically decreased aggregation rate of the protein, confirming the propensity of aromatic residues to promote this process. Nevertheless, a statistical analysis shows that the measured decrease of aggregation rate following mutation arises predominantly from a reduction of hydrophobicity and intrinsic beta-sheet propensity. This suggests that aromatic residues favor aggregation because of these factors rather than for their aromaticity.

• 出版日期2006-4