Blue autofluorescence in protein aggregates “lighted on” by UV induced oxidation

November 13, 2019

Title

Blue autofluorescence in protein aggregates “lighted on” by UV induced oxidation

Author

A. Fricano, F. Librizzi, E. Rao, C. Alfano, V. Vetri

Year

2019

Journal

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

Abstract

Oxidation of amino acid side chains in protein structure can be induced by UV irradiation leading to critical changes in molecular structure possibly modifying protein stability and bioactivity. Here we show, by using a combination of multiple spectroscopic techniques and Fluorescence Lifetime Imaging, that UV-light exposure induces irreversible oxidation processes in Ubiquitin structure. In particular, the growth of a new autofluorescence peak in the blue region is detected, that we attribute to tyrosine oxidation products. Blue autofluorescence intensity is found to progressively increase also during aggregation processes leading to the formation of aggregates of non-amyloid nature. Significantly, analogous spectral modifications are found in amyloid fibrils from human insulin and Amyloid-β peptide grown under UV exposure. Experimental results reveal a substantial overlap between the fluorescence signal here attributed to tyrosine oxidation and the one referred in literature as “Amyloid autofluorescence”. These findings clearly represent a caveat about the specificity of the blue fluorescence peak measured for amyloids, especially when grown in conditions in which tyrosine residues may be oxidized.Moreover, our results once again highlight the close link between the formation of amyloid aggregates and protein damage resulting from oxidative stress, as these neurotoxic aggregate species are found to contain damaged residues.

Instrument

V-760, J-715, FP-8500

Keywords

Fluorescence, Kinetics, Absorption, Protein structure, Photo stability, Thermal stability, Aggregation, Circular dichroism, Secondary structure, Biochemistry