Structure of toll-like receptors.
The ten human Toll-like receptors are able to respond to an extremely diverse range of microbial products ranging from di- and tri-acylated lipids to nucleic acids. An understanding of the molecular structure adopted by the receptor extracellular, transmembrane, and cytoplasmic domains and the way in which these structures interact with ligands and downstream signaling adapters can explain how recognition and signal transduction are achieved at a molecular level. In this article we discuss how the leucine-rich repeats of the receptor ectodomain have evolved to bind a wide variety of biological molecules. We also discuss how ligand binding induces dimerization of two receptor chains and initiates a series of protein conformational changes that lead to a signaling event in the cytoplasm of the immune system cell. Thus, the signaling process of the TLRs can be viewed as a unidirectional molecular switch.
Gay
Nicholas J
NJ
University of Cambridge, 80, Tennis Court Rd., Cambridge, CB2 1GA, UK. njg11@mole.bio.cam.ac.uk
Gangloff
Monique
M
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000648:ultrastructure; D003593:Cytoplasm / Q000737:chemistry / Q000648:ultrastructure; D005110:Extracellular Space / Q000737:chemistry; D006801:Humans; D008024:Ligands; D009696:Nucleic Acids / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000502:physiology; D051193:Toll-Like Receptors / Q000737:chemistry* / Q000648:ultrastructure
D008024:Ligands; D009696:Nucleic Acids; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors