Structural basis for specific recognition of single-stranded RNA by Toll-like receptor 13

Nat Struct Mol Biol. 2015 Oct;22(10):782-7. doi: 10.1038/nsmb.3080. Epub 2015 Aug 31.


Toll-like receptors (TLRs) have crucial roles in innate immunity, functioning as pattern-recognition receptors. TLR13 recognizes a conserved sequence from bacterial 23S rRNA and then triggers an immune response. Here we report the crystal structure of the mouse TLR13 ectodomain bound by a 13-nt single-stranded (ss) RNA derived from 23S rRNA. The ssRNA induces TLR13 dimerization but assumes a stem-loop-like structure that is completely different from that in the bacterial ribosome but nevertheless is crucial for TLR13 recognition. Most of the RNA nucleotides are splayed out to make base-specific contacts with the concave surface of TLR13, and RNA-specific interactions are important to allow TLR13 to distinguish RNA from DNA. Interestingly, a viral-derived 16-nt ssRNA predicted to form a similar stem-loop-like structure also induces TLR13 activation. Together, our results reveal the structural mechanism of TLR13's sequence- and conformation-specific recognition of ssRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, Gel
  • Cryoelectron Microscopy
  • Crystallization
  • Dimerization
  • Image Processing, Computer-Assisted
  • Luciferases
  • Mice
  • Microscopy, Electron, Transmission
  • Models, Molecular*
  • Oligonucleotides / genetics
  • Protein Binding
  • Protein Conformation
  • RNA, Ribosomal, 23S / chemistry*
  • RNA, Ribosomal, 23S / genetics
  • RNA, Ribosomal, 23S / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Toll-Like Receptors / chemistry*
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism*


  • Oligonucleotides
  • RNA, Ribosomal, 23S
  • Tlr13 protein, mouse
  • Toll-Like Receptors
  • Luciferases

Associated data

  • PDB/4Z0C