| Timetable |
| Download Conference Program |
| Download All Abstracts |
| Zoom Access |
| Corporate Program |
Poster Presentations
Day 4, June 25（Wed.）
Room P (Maesato East, Foyer, Ocean Wing)
- 4P-AM-50
Mass spectrometry reveals the stoichiometric regulation and phosphorylation for early stage activation of NLRP3 inflammasome
(1IBC, Academia Sinica, 2IBS, NTU)
oNing-En Chang1, Yen-Ling Chen1,2, Hsin-Yung Yen1,2
The NLRP3 inflammasome is a key inducer for pyroptosis in the innate immune system. Recent cryo-electron microscopy investigations revealed the architectures of various NLRP3 assemblies and their functional association was suggested. Although the static protein structures provide molecular details of NLRP3 in near-atomic resolution, it remains unclear how NLRP3 transits among different functional states, and a high-resolution method is required to probe the dynamic process of NLRP3 activation.
In this study, we employed high-resolution native mass spectrometry to investigate the stoichiometry modulation of NLRP3 during its activation. Under optimal ion transmission and detection, we successfully acquired the spectra of near mega-Dalton NLRP3 complexes and revealed their unique stoichiometry. The following investigations of protein complexes from cells pre-treated with the activation stimuli further uncovered their disassembly in an ATP-dependent manner, suggesting its important role in NLRP3 activation. Surprisingly, we discovered the unique phosphorylation patterns possessed by disassembled NLRP3 and proposed its priming effect for ATP-induced disassembly. Collectively, our results suggest the molecular processes of NLRP3 for its early-stage activation. The disassembly of NLRP3 complexes induced by ATP and protein phosphorylation plays a role in initiating downstream activation processes, providing a deeper understanding of the molecular mechanisms governing NLRP3 activation.