PDBsum entry 3w3l

Immune system

PDB id: 3w3l

Contents

Protein chain

751 a.a.

Ligands

NAG-NAG-BMA-MAN-MAN ×8

NAG-NAG-BMA ×4

NAG ×15

SO4 ×8

RX8 ×4

Waters ×895

PDB id:

3w3l

Name:

Immune system

Title:

Crystal structure of human tlr8 in complex with resiquimod (r848) crystal form 1

Structure:

Toll-like receptor 8. Chain: a, b, c, d. Fragment: unp residues 27-827. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tlr8, unq249/pro286. Expressed in: drosophila. Expression_system_taxid: 7215.

Resolution:

2.33Å R-factor: 0.198 R-free: 0.239

Authors:

H.Tanji,U.Ohto,T.Shimizu

Key ref:

H.Tanji et al. (2013). Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands. Science, 339, 1426-1429. PubMed id: 23520111 DOI: 10.1126/science.1229159

Date:

22-Dec-12 Release date: 03-Apr-13

Protein chains

Q9NR97  (TLR8_HUMAN) -  Toll-like receptor 8 from Homo sapiens

Seq: 1041 a.a.

Struc: 751 a.a.

DOI no: 10.1126/science.1229159

Science 339:1426-1429 (2013)

PubMed id: 23520111

Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands.

H.Tanji, U.Ohto, T.Shibata, K.Miyake, T.Shimizu.

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.