Effect of fibrillation on the excited state dynamics of tryptophan in serum protein – A time-resolved fluorescence study

• Understanding the water relaxation dynamics in HSA amyloid fibril.
• Despite having more ordered structure, tryptophan in fibril experiences more labile water.
• Microheterogeneity in the protein increases on fibrillation.

The aggregation of proteins into the amyloid fibrils is mainly responsible for several neurological diseases. Knowledge of dynamics in amyloid fibril is very essential to understand its biological activity. Although, the effects of environment like pH, ionic strength, temperature, etc. on the fibril have been studied extensively, studies on the dynamics of amyloid fibril and the role of water in fibril are scarce. In this article, we have reported the results on the excited state dynamics of amyloid fibrils formed by a well-known blood plasma protein, human serum albumin (HSA), at neutral pH. The sole tryptophan residue, W214, has been used as the intrinsic fluorescent probe to monitor its excited state dynamics. Steady-state and time-resolved fluorescence data suggests that the W214 becomes more closer to the quencher amino acid residues in the fibrillar phase than in the native protein. From detailed time-resolved emission measurements, it is shown that despite having a more ordered structure, the water molecules around W214 in amyloid fibril is more labile than that in the native protein. Fluorescence depolarization studies also indicate that the W214 residue is located in a relatively more flexible region of the ordered amyloid fibril than that in the native protein.

Solvent relaxation dynamics in amyloid fibril.Figure optionsDownload as PowerPoint slide