Toll-like receptors as molecular switches

Nat Rev Immunol. 2006 Sep;6(9):693-8. doi: 10.1038/nri1916. Epub 2006 Aug 18.


Members of the Toll family of single-pass transmembrane receptors are key mediators of innate immunity in both vertebrates and invertebrates. They respond to various pathogen-associated stimuli and transduce the complex signalling responses that are required for inflammation and for the subsequent development of adaptive immunity. Here, we propose a molecular mechanism for signalling by the Toll and Toll-like receptors that involves a series of protein conformational changes initiated by dimerization of their extracellular domains. The initial dimerization event, which is triggered by the interaction of the receptor with its ligand, might disrupt a pre-formed but non-functional dimer. Formation of a stable receptor-ligand complex then relieves constitutive autoinhibition, enabling receptor-receptor association of the extracellular juxtamembrane regions and cytoplasmic signalling domains. This activation process constitutes a tightly regulated, unidirectional molecular switch.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Ligands
  • Models, Molecular
  • Protein Binding
  • Signal Transduction*
  • Toll-Like Receptors / chemistry
  • Toll-Like Receptors / immunology*
  • Toll-Like Receptors / metabolism*


  • Ligands
  • Toll-Like Receptors