The ability of the immune system to recognize molecules that are broadly shared by pathogens is, in part, due to the presence of immune receptors called toll-like receptors (TLRs) that are expressed on the membranes of leukocytes including dendritic cells, macrophages, natural killer cells, cells of the adaptive immunity T cells, and B cells, and non-immune cells (epithelial and endothelial cells, and fibroblasts). The binding of ligands - either in the form of adjuvant used in vaccinations or in the form of invasive moieties during times of natural infection - to the TLR marks the key molecular events that ultimately lead to innate immune responses and the development of antigen-specific acquired immunity. Upon activation, TLRs recruit adaptor proteins (proteins that mediate other protein-protein interactions) within the cytosol of the immune cell to propagate the antigen-induced signal transduction pathway. These recruited proteins are then responsible for the subsequent activation of other downstream proteins, including protein kinases (IKKi, IRAK1, IRAK4, and TBK1) that further amplify the signal and ultimately lead to the upregulation or suppression of genes that orchestrate inflammatory responses and other transcriptional events. The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13. TLR3 does not use the MyD88 dependent pathway. Its ligand is retroviral double-stranded RNA (dsRNA), which activates the TRIF dependent signalling pathway. Upon binding to the viral dsRNA, TLR3 forms clusters that extend along the viral genome. Here you can see how the structure of these clusters look like, as determined by cryoEM (PDB code: 7WV3)

#molecularart ... #immolecular ... #tlr3 ... #receptor ... #immunity ... #dsrna ... #virus ... #cluster ... #cryoem

Structure rendered with @proteinimaging and depicted with @corelphotopaint