3W3K

Crystal structure of human TLR8 in complex with CL075

Summary for 3W3K

• Entry DOI: 10.2210/pdb3w3k/pdb
• Related: 3W3G 3W3J 3W3L 3W3M 3W3N
• Descriptor: Toll-like receptor 8, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: leucine rich repeat, rna, glycosylation, rna recognition, ssrna, receptor, rna receptor, innate immunity, rna binding, secreted, cl075, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 192138.87

Authors

Tanji, H.,Ohto, U.,Shimizu, T. (deposition date: 2012-12-22, release date: 2013-04-03, Last modification date: 2024-10-16)

Primary citation

Tanji, H.,Ohto, U.,Shibata, T.,Miyake, K.,Shimizu, T.
Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands
Science, 339:1426-1429, 2013

PubMed Abstract: 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.

PubMed: 23520111
DOI: 10.1126/science.1229159

Experimental method

X-RAY DIFFRACTION (2.3 Å)