The structural biology of Toll-like receptors

Structure. 2011 Apr 13;19(4):447-59. doi: 10.1016/j.str.2011.02.004.


The membrane-bound Toll-like receptors (TLRs) trigger innate immune responses after recognition of a wide variety of pathogen-derived compounds. Despite the wide range of ligands recognized by TLRs, the receptors share a common structural framework in their extracellular, ligand-binding domains. These domains all adopt horseshoe-shaped structures built from leucine-rich repeat motifs. Typically, on ligand binding, two extracellular domains form an "m"-shaped dimer sandwiching the ligand molecule bringing the transmembrane and cytoplasmic domains in close proximity and triggering a downstream signaling cascade. Although the ligand-induced dimerization of these receptors has many common features, the nature of the interactions of the TLR extracellular domains with their ligands varies markedly between TLR paralogs.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Tertiary*
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Toll-Like Receptors / chemistry*
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism*


  • Toll-Like Receptors