TLR3

Toll-like receptor 3 (TLR3) also known as CD283 (is_associated_with::cluster of differentiation 283) is a is_associated_with::protein that in humans is encoded by the TLR3 is_associated_with::gene. TLR3 is a member of the is_associated_with::Toll-like receptor family of is_associated_with::pattern recognition receptors of the is_associated_with::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 is_associated_with::cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This receptor is most abundantly expressed in is_associated_with::placenta and is_associated_with::pancreas, and is restricted to the is_associated_with::dendritic subpopulation of the is_associated_with::leukocytes. It recognizes dsRNA associated with viral infection, and induces the activation of is_associated_with::IRF3, unlike all other Toll-like receptors which activate is_associated_with::NF-κB. is_associated_with::IRF3 ultimately induces the production of type I is_associated_with::interferons. It may thus play a role in host defense against viruses.

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

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

Structure
The structure of TLR3 was reported in June 2005 by researchers at is_associated_with::The Scripps Research Institute. 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 is_associated_with::sugar molecules, making it a is_associated_with::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 is_associated_with::amino acids, which may be a binding site for negatively charged double-stranded RNA.

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