Structural basis for the oligomerization-mediated regulation of NLRP3 inflammasome activation.
Proc Natl Acad Sci U S A
; 119(11): e2121353119, 2022 03 15.
Article
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| MEDLINE
| ID: mdl-35254907
ABSTRACT
SignificanceThe nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) is a pattern recognition receptor that forms an inflammasome. The cryo-electron microscopy structure of the dodecameric form of full-length NLRP3 bound to the clinically relevant NLRP3-specific inhibitor MCC950 has established the structural basis for the oligomerization-mediated regulation of NLRP3 inflammasome activation and the mechanism of action of the NLRP3 specific inhibitor. The inactive NLRP3 oligomer represents the NLRP3 resting state, capable of binding to membranes and is likely disrupted for its activation. Visualization of the inhibitor binding mode will enable optimization of the activity of NLRP3 inflammasome inhibitor drugs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Multimerización de Proteína
/
Inflamasomas
/
Proteína con Dominio Pirina 3 de la Familia NLR
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón