Dusquetide modulates innate immune response through binding to p62.
Structure
; 30(8): 1055-1061.e7, 2022 08 04.
Article
en En
| MEDLINE
| ID: mdl-35640615
ABSTRACT
SQSTM1/p62 is an autophagic receptor that plays a major role in mediating stress and innate immune responses. Preclinical studies identified p62 as a target of the prototype innate defense regulator (IDR); however, the molecular mechanism of this process remains unclear. Here, we describe the structural basis and biological consequences of the interaction of p62 with the next generation of IDRs, dusquetide. Both electrostatic and hydrophobic contacts drive the formation of the complex between dusquetide and the ZZ domain of p62. We show that dusquetide penetrates the cell membrane and associates with p62 in vivo. Dusquetide binding modulates the p62-RIP1 complex, increases p38 phosphorylation, and enhances CEBP/B expression without activating autophagy. Our findings provide molecular details underlying the IDR action that may help in the development of new strategies to pharmacologically target p62.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Inmunidad Innata
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Structure
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Año:
2022
Tipo del documento:
Article