Toll-like receptors

Toll-like receptors show homology with the Drosophila Toll protein and the human interleukin-1 receptor family, and are transmembrane proteins that recognize extracellular or endosomal pathogen-associated molecular patterns. The specificity of Toll-like receptor signaling is due to adaptor proteins containing Toll–interleukin 1 receptor (TIR) domains. Five TIR adaptors display activating functions: MyD88, Mal, TRIF, TRAM, and SARM.

The TLR family is characterized by the presence of leucine-rich repeats (which mediates ligand binding) and a Toll/interleukin-1 receptor-like domain (which mediates interaction with intracellular signaling proteins). Most identified TLR ligands are either conserved microbial products that signal the presence of an infection, or endogenous ligands that might signal other danger conditions. TLRs trigger signals evoking synthesis and secretion of cytokines and activation of host defenses through NF-κB, MAP kinases, and costimulatory molecules.

receptor

ligand

adaptor proteins

TLR1 triacyl lipoproteins MyD88/MAL
TLR2 lipoproteins; G+ peptidoglycan; lipoteichoic acids; fungi; viral glycoproteins MyD88/MAL
TLR3 double-stranded RNA (viruses), poly I:C TRIF
TLR4 lipopolysaccharide (LPS); viral glycoproteins MyD88/MAL/TRIF/TRAM
TLR5 flagellin MyD88
TLR6 diacyl lipoproteins MyD88/MAL
TLR7 small synthetic compounds; single-stranded RNA MyD88
TLR8 small synthetic compounds; single-stranded RNA MyD88
TLR9 unmethylated CpG DNA MyD88
TLR10 unknown unknown
TLR11 profilin MyD88
TLR12 unknown unknown
TLR13 unknown unknown

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