The interaction between NLRP1 and oxidized TRX1 involves a transient disulfide bond.
Cell Chem Biol
; 31(5): 955-961.e4, 2024 May 16.
Article
em En
| MEDLINE
| ID: mdl-38215746
ABSTRACT
NLRP1 is an innate immune receptor that detects pathogen-associated signals, assembles into a multiprotein structure called an inflammasome, and triggers a proinflammatory form of cell death called pyroptosis. We previously discovered that the oxidized, but not the reduced, form of thioredoxin-1 directly binds to NLRP1 and represses inflammasome formation. However, the molecular basis for NLRP1's selective association with only the oxidized form of TRX1 has not yet been established. Here, we leveraged AlphaFold-Multimer, site-directed mutagenesis, thiol-trapping experiments, and mass spectrometry to reveal that a specific cysteine residue (C427 in humans) on NLRP1 forms a transient disulfide bond with oxidized TRX1. Overall, this work demonstrates how NLRP1 monitors the cellular redox state, further illuminating an unexpected connection between the intracellular redox potential and the innate immune system.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxirredução
/
Tiorredoxinas
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Proteínas Adaptadoras de Transdução de Sinal
/
Dissulfetos
/
Proteínas NLR
Limite:
Humans
Idioma:
En
Revista:
Cell Chem Biol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos