Chemoproteomic Identification of Blue-Light-Damaged Proteins

Visible light, particularly in the blue region of the spectrum, can cause cell dysfunction through the generation of singlet oxygen, contributing to cellular aging and age-related pathologies. Although photooxidation of nucleic acids, lipids, and amino acids has been extensively studied, the magnitude and span of blue-light-induced protein damages within proteome remain largely unknown. Herein we present a chemoproteomic approach to mapping blue-light-damaged proteins in live mammalian cells by exploiting a nucleophilic alkyne chemical probe. A gene ontology enrichment analysis revealed that cell surface proteins are more readily oxidized than other susceptible sets of proteins, including mitochondrial proteins. In particular, the integrin family of cell surface receptors (ITGs) was highly ranked in the mammalian cells tested, including human corneal endothelial cells. The blue-light-oxidized ITGB1 protein was functionally inactive in promoting cell adhesion and proliferation, suggesting that the photodamage of integrins contributes to the blue-light-induced cell dysfunction. Further application of our method to various cells and tissues should lead to a comprehensive analysis of light-sensitive proteins.

Automated summary

Research has shown that visible light, especially in the blue region, can cause cell dysfunction and contribute to cellular aging and age-related pathologies by generating singlet oxygen. A chemoproteomic approach has been used to map blue-light-damaged proteins in live mammalian cells, revealing that cell surface proteins are more prone to oxidation compared to other susceptible proteins. The integrin family of cell surface receptors, including ITGB1, was found to be highly impacted, leading to loss of functionality in cell adhesion and proliferation. This study highlights the importance of understanding light-induced protein damages and their effects on cellular functions.