Viral DNA Binding to NLRC3, an Inhibitory Nucleic Acid Sensor, Unleashes STING, a Cyclic Dinucleotide Receptor that Activates Type I Interferon. | Academic Article individual record
abstract

Immune suppression is a crucial component of immunoregulation and a subgroup of nucleotide-binding domain (NBD), leucine-rich repeat (LRR)-containing proteins (NLRs) attenuate innate immunity. How this inhibitory function is controlled is unknown. A key question is whether microbial ligands can regulate this inhibition. NLRC3 is a negative regulator that attenuates type I interferon (IFN-I) response by sequestering and attenuating stimulator of interferon genes (STING) activation. Here, we report that NLRC3 binds viral DNA and other nucleic acids through its LRR domain. DNA binding to NLRC3 increases its ATPase activity, and ATP-binding by NLRC3 diminishes its interaction with STING, thus licensing an IFN-I response. This work uncovers a mechanism wherein viral nucleic acid binding releases an inhibitory innate receptor from its target.

authors
author list (cited authors)
Li, X., Deng, M., Petrucelli, A. S., Zhu, C., Mo, J., Zhang, L. u., ... Ting, J.
publication date
2019
publisher
Elsevier bv Publisher
published in
IMMUNITY Journal
keywords
  • Membrane Proteins
  • Tbk1
  • Animals
  • Cell Line, Tumor
  • Mice, Inbred C57BL
  • DNA, Viral
  • Mice
  • Nucleic Acids
  • Hela Cells
  • Sting
  • Intercellular Signaling Peptides And Proteins
  • Dna-binding Receptor
  • Interferon Type I
  • Protein Binding
  • Cell Line
  • Immunity, Innate
  • Nod-like Receptor
  • Interferon
  • Humans
  • HEK293 Cells
altmetric score

24.75

citation count

8