3W3L

Crystal structure of human TLR8 in complex with Resiquimod (R848) crystal form 1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.33 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.198 

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Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

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

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

(2013) Science 339: 1426-1429

  • DOI: https://doi.org/10.1126/science.1229159
  • Primary Citation of Related Structures:  
    3W3G, 3W3J, 3W3K, 3W3L, 3W3M, 3W3N

  • 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.


  • Organizational Affiliation

    Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Toll-like receptor 8
A, B, C, D
811Homo sapiensMutation(s): 0 
Gene Names: TLR8UNQ249/PRO286
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NR97 (Homo sapiens)
Explore Q9NR97 
Go to UniProtKB:  Q9NR97
PHAROS:  Q9NR97
GTEx:  ENSG00000101916 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9NR97
Glycosylation
Glycosylation Sites: 7Go to GlyGen: Q9NR97-1
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
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
E, G, H, J, K
E, G, H, J, K, M, N, P
5N-Glycosylation
Glycosylation Resources
GlyTouCan:  G22768VO
GlyCosmos:  G22768VO
GlyGen:  G22768VO
Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
F, I, L, O
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
RX8
Query on RX8

Download Ideal Coordinates CCD File 
AA [auth B],
EA [auth C],
JA [auth D],
KA [auth D]
1-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol
C17 H22 N4 O2
BXNMTOQRYBFHNZ-UHFFFAOYSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
FA [auth C]
GA [auth C]
HA [auth C]
LA [auth D]
MA [auth D]
FA [auth C],
GA [auth C],
HA [auth C],
LA [auth D],
MA [auth D],
NA [auth D],
OA [auth D],
Q [auth A],
R [auth A],
S [auth A],
T [auth A],
W [auth B],
X [auth B],
Y [auth B],
Z [auth B]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
BA [auth B]
CA [auth B]
DA [auth B]
IA [auth C]
PA [auth D]
BA [auth B],
CA [auth B],
DA [auth B],
IA [auth C],
PA [auth D],
QA [auth D],
U [auth A],
V [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
RX8 BindingDB:  3W3L EC50: min: 363, max: 9600 (nM) from 10 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.33 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.198 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.47α = 90
b = 138.87β = 92.43
c = 169.661γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-04-03
    Type: Initial release
  • Version 1.1: 2018-06-13
    Changes: Data collection, Derived calculations
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Database references, Derived calculations, Structure summary
  • Version 2.1: 2024-10-30
    Changes: Data collection, Database references, Structure summary