TLR8 dimer binds TLR7, TLR8 ligands

Stable Identifier
Reaction [binding]
Homo sapiens
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Endosomal recognition of viral single stranded (ss) RNA and imidazoquinoline compounds occurs by means of TLR7 and TLR8. Structural analyses have revealed that both TLR7 and TLR8 possess two binding sites which do not share the same specificities (Zhang Z et al. 2016). The binding site 1 is highly conserved between TLR7 and TLR8 and binds nucleosides (guanosine (G) for TLR7 and uridine (U) for TLR8) or base analogs. Binding site 2 of TLR7 and TLR8 is less conserved and binds ssRNA with U(U) and U(G) motifs. TLR7 acts as a dual receptor for G and U-containing ssRNAs. Binding of ssRNA to the site 2 of TLR7 strongly enhances the interaction of TLR7 and G at the first site leading to subsequent receptor dimerization. Conversely, chemical ligands are adequately potent to induce TLR7 dimerization by binding to the first site alone (Zhang Z et al. 2016, 2018). Further, upon ligand stimulation, the TLR8 dimer was reorganized such that the two C termini were brought into proximity (Tanji H et al. 2013). The loop between leucine-rich repeat 14 (LRR14) and LRR15 was cleaved; however, the N- and C-terminal halves remained associated and contributed to ligand recognition and dimerization, which enables downstream signaling processes (Tanji H et al. 2013, 2016).

Literature References
PubMed ID Title Journal Year
14976261 Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA

Diebold, SS, Kaisho, T, Hemmi, H, Akira, S, Reis e Sousa, C

Science 2004
12032557 Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848

Jurk, M, Heil, F, Vollmer, J, Schetter, C, Krieg, AM, Wagner, H, Lipford, G, Bauer, S

Nat Immunol 2002
23123977 Extraordinary GU-rich single-strand RNA identified from SARS coronavirus contributes an excessive innate immune response

Li, Y, Chen, M, Cao, H, Zhu, Y, Zheng, J, Zhou, H

Microbes Infect. 2013
11812998 Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway

Hemmi, H, Kaisho, T, Takeuchi, O, Sato, S, Sanjo, H, Hoshino, K, Horiuchi, T, Tomizawa, H, Takeda, K, Akira, S

Nat Immunol 2002
14976262 Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8

Heil, F, Hemmi, H, Hochrein, H, Ampenberger, F, Kirschning, C, Akira, S, Lipford, G, Wagner, H, Bauer, S

Science 2004
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