The interaction between NLRP1 and oxidized TRX1 involves a transient disulfide bond.
Cell Chem Biol
; 31(5): 955-961.e4, 2024 May 16.
Article
en 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oxidación-Reducción
/
Tiorredoxinas
/
Proteínas Adaptadoras Transductoras de Señales
/
Disulfuros
/
Proteínas NLR
Límite:
Humans
Idioma:
En
Revista:
Cell Chem Biol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos