Paired-probe chemoproteomic strategy enables global site-resolved quantification of lysine redox states
Site-specific quantification of lysine (Lys) redox states remains unexplored, as current approaches identify only a limited number of modification sites without determining their stoichiometry. Allysine, an oxidized form of Lys, provides a model posttranslational modification (PTM) for addressing this challenge by requiring selective enrichment and site-specific stoichiometric quantification.…
Researchers have developed a groundbreaking technique to precisely measure the redox states of lysine, an amino acid crucial for protein function, at a cellular level. Traditionally, scientists could only identify a few lysine modification sites without knowing their stoichiometry, or the ratio of different modifications. To overcome this limitation, a team of scientists created a quantitative chemoproteomic platform called PRISM-Lys.
PRISM-Lys employs a unique paired-probe strategy using two complementary Am-alkyne and Ald-alkyne probes. These probes work together in identical reactions, generating the same chemical product, which enables selective enrichment of allysine, the oxidized form of lysine, and site-specific quantification of lysine redox states. This innovative approach allows for global, site-resolved analysis of lysine redox states across various biological samples, including cells and tissues.
Using PRISM-Lys, researchers observed that lysine oxidation events undergo bidirectional, site-selective remodeling during the process of ferroptosis, a type of cell death associated with iron accumulation and lipid peroxidation. By providing a new quantitative perspective on protein oxidation, PRISM-Lys opens up new avenues for investigating the role of lysine redox states in various biological systems and diseases.
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