Toward a structural understanding of nucleic acid-sensing Toll-like receptors in the innate immune system

FEBS Lett. 2017 Oct;591(20):3167-3181. doi: 10.1002/1873-3468.12749. Epub 2017 Jul 21.

Abstract

The history of mankind has been plagued by the tug of war with viral infections. Toll-like receptors (TLRs) and other receptors of the innate immune system constitute an early defense system against invading viruses by recognizing the viral genetic material, the nucleic acids (NAs). Agonistic ligands of NA-sensing TLRs play an emerging role in the treatment of viral diseases, demonstrating a crucial role of these receptors. Recently, crystal structures have afforded new insights into TLR recognition of NAs. An aberrant activation by self-NAs, which leads to the inflammation and autoimmunity, is avoided by strict regulation of NA-TLR interaction at multiple check-points. This Review summarizes the novel structural understanding of NA-sensing by TLRs and regulatory mechanisms of these receptors.

Keywords: Toll-like receptor; innate immunity; nucleic acid sensor.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity
  • Gene Expression Regulation
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Immunity, Innate*
  • Nucleic Acid Conformation
  • Nucleic Acids / chemistry*
  • Nucleic Acids / immunology
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • Signal Transduction
  • Toll-Like Receptors / chemistry*
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology
  • Virus Diseases / genetics
  • Virus Diseases / immunology*
  • Virus Diseases / virology
  • Viruses / growth & development
  • Viruses / immunology

Substances

  • Nucleic Acids
  • Toll-Like Receptors

Associated data

  • PDB/1ZIW
  • PDB/3WPB
  • PDB/3WPG
  • PDB/3W3G
  • PDB/4R07
  • PDB/3CIY
  • PDB/5GMF
  • PDB/4Z0C
  • PDB/3W3N
  • PDB/5GMH