3W3M: Crystal Structure Of Human Tlr8 In Complex With Resiquimod (r848) Crystal Form 2

Citation:
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.
PDB ID: 3W3MDownload
MMDB ID: 108791
PDB Deposition Date: 2012/12/22
Updated in MMDB: 2013/04
Experimental Method:
x-ray diffraction
Resolution: 2.7  Å
Source Organism:
Similar Structures:
Biological Unit for 3W3M: dimeric; determined by author and by software (PISA)
Molecular Components in 3W3M
Label Count Molecule
Proteins (2 molecules)
2
Toll-like Receptor 8(Gene symbol: TLR8)
Molecule annotation
Chemicals (28 molecules)
1
2
2
18
3
4
4
2
5
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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