Identification of Skp1 as a target of mercury sulfide for neuroprotection
CHEMICAL COMMUNICATIONS(2024)
摘要
Mercury sulfide (HgS) exerts extensive biological effects on neuronal function. To investigate the direct target of HgS in neuronal cells, we developed a biotin-tagged HgS probe (bio-HgS) and employed an affinity purification technique to capture its target proteins. Then, we identified S-phase kinase-associated protein 1 (Skp1) as a potential target of HgS. Unexpectedly, we discovered that HgS covalently binds to Skp1 through a "Cys62-HgS-Cys120" mode. Moreover, our findings revealed that HgS inhibits the ubiquitin-protease system through Skp1 to up-regulate SNAP-25 expression, thereby triggering synaptic vesicle exocytosis to regulate locomotion ability in C. elegans. Collectively, our findings may promote a comprehensive interpretation of the pharmacological mechanism of mercury sulfide on neuroprotective function. We designed a biotin-tagged HgS probe and identified S-phase kinase-associated protein 1 (Skp1) as the target protein of HgS. HgS selectively binds to Skp1 in a "Cys-HgS-Cys" mode.
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