Leucine-rich repeats and pathogen recognition in Toll-like receptors

Trends Immunol. 2003 Oct;24(10):528-33. doi: 10.1016/s1471-4906(03)00242-4.


Toll-like receptors (TLRs) are the major cell-surface initiators of inflammatory responses to pathogens. They bind a wide variety of pathogenic substances through their ectodomains (ECDs). Here, we ask: what is the structural basis for this interaction? Toll-like receptor ECDs comprise 19-25 tandem copies of a motif known as the leucine-rich repeat (LRR). No X-ray structure of a TLR-ECD is currently available but there are several high-resolution LRR-containing proteins that can be used to model TLRs. We suggest that the basic framework of TLRs is a horseshoe-shaped solenoid that contains an extensive beta-sheet on its concave surface, and numerous ligand-binding insertions. Together, these insertions and the beta-sheet could provide a binding surface that is 10-fold greater in area than binding surfaces in antibodies and T-cell receptors.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Humans
  • Immunity, Cellular*
  • Leucine
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / immunology
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Receptors, Cell Surface / chemistry*
  • Receptors, Cell Surface / immunology
  • Repetitive Sequences, Amino Acid
  • Sequence Alignment
  • Toll-Like Receptors


  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Toll-Like Receptors
  • Leucine