RIG-I Selectively Discriminates against 5'-Monophosphate RNA.
Cell Rep
; 26(8): 2019-2027.e4, 2019 02 19.
Article
en En
| MEDLINE
| ID: mdl-30784585
ABSTRACT
The innate immune sensor RIG-I must sensitively detect and respond to viral RNAs that enter the cytoplasm, while remaining unresponsive to the abundance of structurally similar RNAs that are the products of host metabolism. In the case of RIG-I, these viral and host targets differ by only a few atoms, and a molecular mechanism for such selective differentiation has remained elusive. Using a combination of quantitative biophysical and immunological studies, we show that RIG-I, which is normally activated by duplex RNAs containing a 5'-tri- or diphosphate (5'-ppp or 5'-pp RNAs), is actively antagonized by RNAs containing 5'-monophosphates (5'-p RNAs). This is accomplished by a gating mechanism in which an alternative RIG-I conformation blocks the C-terminal domain (CTD) upon 5'-p RNA binding, thereby short circuiting the activation of signaling.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
ARN Viral
/
Proteína 58 DEAD Box
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos