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Publication Abstract from PubMed

Toll-like receptor 7 (TLR7) and TLR8 recognize single-stranded RNA and initiate innate immune responses. Several synthetic agonists of TLR7-TLR8 display novel therapeutic potential; however, the molecular basis for ligand recognition and activation of signaling by TLR7 or TLR8 is largely unknown. In this study, the crystal structures of unliganded and ligand-induced activated human TLR8 dimers were elucidated. Ligand recognition was mediated by a dimerization interface formed by two protomers. Upon ligand stimulation, the TLR8 dimer was reorganized such that the two C termini were brought into proximity. 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. Thus, ligand binding induces reorganization of the TLR8 dimer, which enables downstream signaling processes.

Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands.,Tanji H, Ohto U, Shibata T, Miyake K, Shimizu T Science. 2013 Mar 22;339(6126):1426-9. doi: 10.1126/science.1229159. PMID:23520111^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.