Structural biology of the Toll-like receptor family

Annu Rev Biochem. 2011;80:917-41. doi: 10.1146/annurev-biochem-052909-141507.


Innate immune receptors respond to common structural patterns in microbial molecules and are called pattern recognition receptors. Toll-like receptors (TLRs) play critical roles in the innate immune system by recognizing microbial lipids, carbohydrates, nucleic acids, and proteins. Precise definition of the ligand "pattern" of TLRs has been difficult to determine primarily owing to a lack of high-resolution structures. Recently, the structures of several TLR-ligand complexes and the intracellular signaling domains have been determined by X-ray crystallography. This new structural information, combined with extensive biochemical and immunological data accumulated over decades, sheds new light on ligand-recognition and -activation mechanisms. In this review, we summarize the TLR structures and discuss proposed ligand-recognition and -activation mechanisms.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Immunity, Innate
  • Ligands
  • Lipopolysaccharides / immunology
  • Lymphocyte Antigen 96 / chemistry
  • Lymphocyte Antigen 96 / genetics
  • Lymphocyte Antigen 96 / immunology
  • Models, Molecular
  • Phylogeny
  • Protein Conformation*
  • Protein Multimerization
  • Toll-Like Receptors / chemistry*
  • Toll-Like Receptors / classification
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology


  • Ligands
  • Lipopolysaccharides
  • Lymphocyte Antigen 96
  • Toll-Like Receptors