4R07

Crystal structure of human TLR8 in complex with ORN06


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.190 

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Ligand Structure Quality Assessment 


This is version 2.0 of the entry. See complete history


Literature

Toll-like receptor 8 senses degradation products of single-stranded RNA

Tanji, H.Ohto, U.Shibata, T.Taoka, M.Yamauchi, Y.Isobe, T.Miyake, K.Shimizu, T.

(2015) Nat Struct Mol Biol 22: 109-115

  • DOI: https://doi.org/10.1038/nsmb.2943
  • Primary Citation of Related Structures:  
    4R07, 4R08, 4R09, 4R0A

  • PubMed Abstract: 

    Toll-like receptor 8 (TLR8) recognizes viral or bacterial single-stranded RNA (ssRNA) and activates innate immune systems. TLR8 is activated by uridine- and guanosine-rich ssRNA as well as by certain synthetic chemicals; however, the molecular basis for ssRNA recognition has remained unknown. In this study, to elucidate the recognition mechanism of ssRNA, we determined the crystal structures of human TLR8 in complex with ssRNA. TLR8 recognized two degradation products of ssRNA—uridine and a short oligonucleotide—at two distinct sites: uridine bound the site on the dimerization interface where small chemical ligands are recognized, whereas short oligonucleotides bound a newly identified site on the concave surface of the TLR8 horseshoe structure. Site-directed mutagenesis revealed that both binding sites were essential for activation of TLR8 by ssRNA. These results demonstrate that TLR8 is a sensor for both uridine and a short oligonucleotide derived from RNA.


  • Organizational Affiliation

    Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, 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
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
E
4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G81315DD
GlyCosmos:  G81315DD
GlyGen:  G81315DD
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, H, I, L, M
F, H, I, L, M, N, O
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
G, J, P
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 5
MoleculeChains Length2D Diagram Glycosylation3D Interactions
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
K
4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G22573RC
GlyCosmos:  G22573RC
GlyGen:  G22573RC
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
UCG
Query on UCG

Download Ideal Coordinates CCD File 
FA [auth C],
LA [auth D],
R [auth A],
Y [auth B]
3'-O-[(R)-{[(2R,3aR,4R,6R,6aR)-6-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-2-hydroxy-2-oxidotetrahydrofuro[3,4-d][1,3,2]dioxaphosphol-4-yl]methoxy}(hydroxy)phosphoryl]uridine 5'-(dihydrogen phosphate)
C19 H24 N7 O18 P3
UIVVUPHFWRPLKC-VMIOUTBZSA-N
URI
Query on URI

Download Ideal Coordinates CCD File 
EA [auth C],
KA [auth D],
Q [auth A],
X [auth B]
URIDINE
C9 H12 N2 O6
DRTQHJPVMGBUCF-XVFCMESISA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
AA [auth B]
BA [auth B]
CA [auth B]
DA [auth B]
GA [auth C]
AA [auth B],
BA [auth B],
CA [auth B],
DA [auth B],
GA [auth C],
HA [auth C],
IA [auth C],
JA [auth C],
MA [auth D],
NA [auth D],
OA [auth D],
PA [auth D],
S [auth A],
T [auth A],
U [auth A],
V [auth A],
W [auth A],
Z [auth B]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
URI Binding MOAD:  4R07 Kd: 5.50e+4 (nM) from 1 assay(s)
UCG Binding MOAD:  4R07 Kd: 4800 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.190 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.66α = 90
b = 141.12β = 90.59
c = 169.53γ = 90
Software Package:
Software NamePurpose
MOLREPphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-01-14
    Type: Initial release
  • Version 1.1: 2015-02-18
    Changes: Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Database references, Derived calculations, Structure summary