Toll-like receptor 1

The binding of ligands to TLR1 activates intracellular signaling cascades leading to an inflammatory response and initiation of immune processes. TLR1 cooperates with TLR2 in the recognition of bacterial triacyl lipoproteins. TLR1 has been shown to recognize the outer surface lipoprotein of Borrelia burgdorferi. The important role of TLR1 in recognizing triacyl lipopeptides has been shown in TLR1-deficient mice. Toll-like receptors, including TLR-1, found on the epithelial cell layer that lines the small and large intestine are important players in the management of the gut microbiota and detection of pathogens. == Expression ==

TLR1 is synthesized in the endoplasmic reticulum. The trafficking of TLR1 from endoplasmic reticulum is controlled by protein associated with TLR4 (PRAT4A), which is endoplasmic reticulum resident chaperone. TLR1 is then transported to Golgi complex and to cell membrane. TLR1 mRNA was expressed at high levels in the kidney, lung, and spleen in adult humans, but in low levels in fetal brain and liver as well as in HeLa cell line. TLR1 is expressed in the highest levels on NK cells compared to other TLRs. TLR1 has been found to be expressed on human peripheral blood γδT cells, myeloid-derived suppressor cells, platelets, CD4+ T cells, microglia, astrocytes, immature dendritic cells, LTi-like innate lymphoid cells It is also found on the surface of macrophages and neutrophils. == Structure ==

TLR1 is a type I transmembrane glycoprotein composed of extracellular, transmembrane and intracellular domains. The intracellular domain of TLR1 consists of a toll/interleukin-1 receptor (TIR) domain, which is shared by various adaptor proteins involved in the signaling cascade initiated by TLRs. The TIR domain of TLR1 has been found as a monomer in the crystal structure. TLR1 is able to recognize ligands as a complex with TLR2, referred to as TLR2/1 heterodimer. TLR2 can heterodimerize also with TLR6 forming TLR2/6 heterodimer. TLR2/1 adopts an "m"-shaped conformation when interacted with its ligands. The "m" shape conformation is formed by extracellular domains of TLR1 and TLR2, bringing the transmembrane and intracellular domains in close association. This conformational arrangement subsequently triggers a downstream signaling cascade. TLR2/1 specifically recognizes triacyl lipopeptides, whereas TLR2/6 recognizes diacyl lipopeptides. Diacyl and triacyl lipopeptides are present on the bacterial outer membrane. In the case of triacyl lipopeptides, the mechanism behind their recognition lies in the incorporation of two lipid chains into the hydrophobic pocket of TLR2, while the remaining lipid chain inserts into a hydrophobic pocket of TLR1. Regarding TLR6, the hydrophobic pocket is obstructed by the side chains of two phenylalanine residues, resulting in a smaller pocket than in TLR1. This structural difference accounts for the distinct ligand specificities exhibited by TLR2/1 and TLR2/6 heterodimers. == Interactions ==

TLR1 has been shown to interact with TLR2. TLR1 recognizes peptidoglycan and (triacyl) lipopeptides in concert with TLR2 (as a heterodimer). == References ==