Structures of TLR–ligand complexes

Toll-like receptors (TLRs) play central roles in the innate immune response by recognizing conserved structural patterns in diverse microbial molecules. The structures of the extracellular domains of four TLRs and their complexes with ligands have recently been determined by high-resolution X-ray crystallography. In this review, we describe these structures and discuss proposed activation mechanisms. TLRs deviate substantially from the canonical LRR structure and interact with a large variety of ligands in a highly divergent fashion. Agonistic ligands induce the formation of ‘m’ shaped TLR dimers in which the C-termini of the extracellular domains converge in the middle. This structural rearrangement of the extracellular domains suggests an activation mechanism that may be common to all TLR family proteins.