Zinc-responsive labeling in live cells for novel conditional proteomics

Zinc signaling and dynamics play significant roles in many physiological responses and diseases. To understand the physiological roles of zinc in detail, comprehensive identification of proteins under high concentration of mobile zinc ion is crucial. In this report, we developed a novel “conditional proteomics” based on a chemical proteomic strategy with designer zinc-responsive labeling reagents (AIZin). In this conditional proteomics, a subset of proteins in a zinc-rich environment is tagged and identified in combination with quantitative mass spectrometry. This method was successfully applied to elucidate zinc dyshomeostasis induced by nitric oxide-triggered oxidative stress in glioma cells and unveiled dynamic changes of the zinc-related proteomes. Moreover, a subset of protein composition identified by our method allowed the characterization of unknown zinc-rich vesicles generated by oxidative stress as endoplasmic reticulum-Golgi-related vesicles.