TLR3

Toll-like receptor 3
The structure of TLR3 covered with sugars
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1ZIW, 2A0Z, 3ULU, 3ULV
Identifiers
Symbols	TLR3 ; CD283; IIAE2
External IDs	OMIM: 603029 MGI: 2156367 HomoloGene: 20696 IUPHAR: 1753 ChEMBL: 1075113 GeneCards: TLR3 Gene
Gene ontology Molecular function • double-stranded RNA binding • receptor activity • transmembrane signaling receptor activity • protein binding Cellular component • Golgi membrane • cytoplasm • lysosomal membrane • endoplasmic reticulum membrane • integral component of plasma membrane • cell surface • endosome membrane • membrane • endolysosome membrane Biological process • toll-like receptor signaling pathway • microglial cell activation involved in immune response • MyD88-independent toll-like receptor signaling pathway • inflammatory response • hyperosmotic response • signal transduction • I-kappaB kinase/NF-kappaB signaling • activation of NF-kappaB-inducing kinase activity • I-kappaB phosphorylation • male gonad development • detection of virus • positive regulation of chemokine production • positive regulation of interferon-beta production • positive regulation of interleukin-12 production • positive regulation of interleukin-6 production • positive regulation of interleukin-8 production • positive regulation of tumor necrosis factor production • positive regulation of toll-like receptor signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • positive regulation of type III interferon production • cellular response to interferon-beta • TRIF-dependent toll-like receptor signaling pathway • cellular response to drug • positive regulation of NF-kappaB import into nucleus • defense response to bacterium • positive regulation of apoptotic process • positive regulation of I-kappaB kinase/NF-kappaB signaling • response to exogenous dsRNA • positive regulation of interferon-gamma biosynthetic process • positive regulation of chemokine biosynthetic process • innate immune response • positive regulation of interferon-alpha biosynthetic process • positive regulation of interferon-beta biosynthetic process • negative regulation of osteoclast differentiation • positive regulation of transcription from RNA polymerase II promoter • positive regulation of JNK cascade • positive regulation of inflammatory response • positive regulation of NF-kappaB transcription factor activity • defense response to virus • pathogen-associated molecular pattern dependent induction by symbiont of host innate immune response • cellular response to mechanical stimulus • cellular response to interferon-gamma • cellular response to exogenous dsRNA • extrinsic apoptotic signaling pathway • necroptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7098	142980
Ensembl	ENSG00000164342	ENSMUSG00000031639
UniProt	O15455	Q99MB1
RefSeq (mRNA)	NM_003265	NM_126166
RefSeq (protein)	NP_003256	NP_569054
Location (UCSC)	Chr 4: 186.99 – 187.01 Mb	Chr 8: 45.4 – 45.41 Mb
PubMed search

Toll-like receptor 3 (TLR3) also known as CD283 (cluster of differentiation 283) is a protein that in humans is encoded by the TLR3 gene.^[1] TLR3 is a member of the Toll-like receptor family of pattern recognition receptors of the innate immune system.

Function

TLR3 is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This receptor is most abundantly expressed in placenta and pancreas, and is restricted to the dendritic subpopulation of the leukocytes. It recognizes dsRNA associated with viral infection, and induces the activation of IRF3, unlike all other Toll-like receptors which activate NF-κB. IRF3 ultimately induces the production of type I interferons. It may thus play a role in host defense against viruses.^[2]

TLR3 recognizes double-stranded RNA, a form of genetic information carried by some viruses such as retroviruses. Upon recognition, TLR 3 induces the activation of IRF3 to increase production of type I interferons which signal other cells to increase their antiviral defenses. Double-stranded RNA is also recognised by the cytoplasmic receptors RIG-I and MDA-5.^[3]

TLR3 displays a protective role in mouse models of atherosclerosis,^[4] and activation of TLR3 signaling is associated with ischemic preconditioning-induced protection against brain ischemia.^[5] In addition, TLR3 activators show effects on human vascular cells.^[4]

Structure

The structure of TLR3 was reported in June 2005 by researchers at The Scripps Research Institute.^[6] TLR3 forms a large horseshoe shape that contacts with a neighboring horseshoe, forming a "dimer" of two horseshoes. Much of the TLR3 protein surface is covered with sugar molecules, making it a glycoprotein, but on one face (including the proposed interface between the two horseshoes), there is a large sugar-free surface. This surface also contains two distinct patches rich in positively charged amino acids, which may be a binding site for negatively charged double-stranded RNA.

Despite being a glycoprotein, TLR3 crystallises readily - a prerequisite for structural analysis by x-ray crystallography.

References

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

PDB gallery 1ziw: Human Toll-like Receptor 3 extracellular domain structure  2a0z: The molecular structure of toll-like receptor 3 ligand binding domain