4R07

Crystal structure of human TLR8 in complex with ORN06

PDB DOI: https://doi.org/10.2210/pdb4R07/pdb

Classification: IMMUNE SYSTEM
Organism(s): Homo sapiens
Expression System: Drosophila melanogaster
Mutation(s): No

Deposited: 2014-07-30 Released: 2015-01-14
Deposition Author(s): Tanji, H., Ohto, U., Shibata, T., Taoka, M., Yamauchi, Y., Isobe, T., Miyake, K., Shimizu, T.

Experimental Data Snapshot

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

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 2.1 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

PubMed: 25599397 Search on PubMed
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.

Macromolecule Content

Total Structure Weight: 386.1 kDa
Atom Count: 26,233
Modelled Residue Count: 2,958
Deposited Residue Count: 3,244
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Toll-like receptor 8	A, B, C, D	811	Homo sapiens	Mutation(s): 0 Gene Names: TLR8, UNQ249/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 Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q9NR97
Glycosylation
Glycosylation Sites: 7	Glycosylation Focus chain A Focus chain B Focus chain C Focus chain D	Go to GlyGen: Q9NR97-1
Sequence Annotations Expand
Reference Sequence

Oligosaccharides

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Entity ID: 2
Molecule	Chains	Length	2D Diagram	Glycosylation	3D 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	4		N-Glycosylation	Interactions Focus chain E Interactions & Density Focus chain E
Glycosylation Resources
GlyTouCan: G81315DD GlyCosmos: G81315DD GlyGen: G81315DD

Entity ID: 3
Molecule	Chains	Length	2D Diagram	Glycosylation	3D 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	3		N-Glycosylation	Interactions Focus chain F Focus chain H Focus chain I Focus chain L Focus chain M Focus chain N Focus chain O Interactions & Density Focus chain F Focus chain H Focus chain I Focus chain L Focus chain M Focus chain N Focus chain O
Glycosylation Resources
GlyTouCan: G15407YE GlyCosmos: G15407YE GlyGen: G15407YE

Entity ID: 4
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	G, J, P	2		N-Glycosylation	Interactions Focus chain G Focus chain J Focus chain P Interactions & Density Focus chain G Focus chain J Focus chain P
Glycosylation Resources
GlyTouCan: G42666HT GlyCosmos: G42666HT GlyGen: G42666HT

Entity ID: 5
Molecule	Chains	Length	2D Diagram	Glycosylation	3D 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	4		N-Glycosylation	Interactions Focus chain K Interactions & Density Focus chain K
Glycosylation Resources
GlyTouCan: G22573RC GlyCosmos: G22573RC GlyGen: G22573RC

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
UCG Query on UCG Download Ideal Coordinates CCD File SDF format, chain FA [auth C] SDF format, chain LA [auth D] SDF format, chain R [auth A] SDF format, chain Y [auth B] MOL2 format, chain FA [auth C] MOL2 format, chain LA [auth D] MOL2 format, chain R [auth A] MOL2 format, chain Y [auth B] mmCIF format, chain FA [auth C] mmCIF format, chain LA [auth D] mmCIF format, chain R [auth A] mmCIF format, chain Y [auth B]	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		Interactions Focus chain FA [auth C] Focus chain LA [auth D] Focus chain R [auth A] Focus chain Y [auth B] Interactions & Density Focus chain FA [auth C] Focus chain LA [auth D] Focus chain R [auth A] Focus chain Y [auth B]
URI Query on URI Download Ideal Coordinates CCD File SDF format, chain EA [auth C] SDF format, chain KA [auth D] SDF format, chain Q [auth A] SDF format, chain X [auth B] MOL2 format, chain EA [auth C] MOL2 format, chain KA [auth D] MOL2 format, chain Q [auth A] MOL2 format, chain X [auth B] mmCIF format, chain EA [auth C] mmCIF format, chain KA [auth D] mmCIF format, chain Q [auth A] mmCIF format, chain X [auth B]	EA [auth C], KA [auth D], Q [auth A], X [auth B]	URIDINE C₉ H₁₂ N₂ O₆ DRTQHJPVMGBUCF-XVFCMESISA-N		Interactions Focus chain EA [auth C] Focus chain KA [auth D] Focus chain Q [auth A] Focus chain X [auth B] Interactions & Density Focus chain EA [auth C] Focus chain KA [auth D] Focus chain Q [auth A] Focus chain X [auth B]
NAG Query on NAG Download Ideal Coordinates CCD File SDF format, chain AA [auth B] SDF format, chain BA [auth B] SDF format, chain CA [auth B] SDF format, chain DA [auth B] SDF format, chain GA [auth C] SDF format, chain HA [auth C] SDF format, chain IA [auth C] SDF format, chain JA [auth C] SDF format, chain MA [auth D] SDF format, chain NA [auth D] SDF format, chain OA [auth D] SDF format, chain PA [auth D] SDF format, chain S [auth A] SDF format, chain T [auth A] SDF format, chain U [auth A] SDF format, chain V [auth A] SDF format, chain W [auth A] SDF format, chain Z [auth B] MOL2 format, chain AA [auth B] MOL2 format, chain BA [auth B] MOL2 format, chain CA [auth B] MOL2 format, chain DA [auth B] MOL2 format, chain GA [auth C] MOL2 format, chain HA [auth C] MOL2 format, chain IA [auth C] MOL2 format, chain JA [auth C] MOL2 format, chain MA [auth D] MOL2 format, chain NA [auth D] MOL2 format, chain OA [auth D] MOL2 format, chain PA [auth D] MOL2 format, chain S [auth A] MOL2 format, chain T [auth A] MOL2 format, chain U [auth A] MOL2 format, chain V [auth A] MOL2 format, chain W [auth A] MOL2 format, chain Z [auth B] mmCIF format, chain AA [auth B] mmCIF format, chain BA [auth B] mmCIF format, chain CA [auth B] mmCIF format, chain DA [auth B] mmCIF format, chain GA [auth C] mmCIF format, chain HA [auth C] mmCIF format, chain IA [auth C] mmCIF format, chain JA [auth C] mmCIF format, chain MA [auth D] mmCIF format, chain NA [auth D] mmCIF format, chain OA [auth D] mmCIF format, chain PA [auth D] mmCIF format, chain S [auth A] mmCIF format, chain T [auth A] mmCIF format, chain U [auth A] mmCIF format, chain V [auth A] mmCIF format, chain W [auth A] mmCIF format, chain Z [auth B]	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		Interactions Focus chain AA [auth B] Focus chain BA [auth B] Focus chain CA [auth B] Focus chain DA [auth B] Focus chain GA [auth C] Focus chain HA [auth C] Focus chain IA [auth C] Focus chain JA [auth C] Focus chain MA [auth D] Focus chain NA [auth D] Focus chain OA [auth D] Focus chain PA [auth D] Focus chain S [auth A] Focus chain T [auth A] Focus chain U [auth A] Focus chain V [auth A] Focus chain W [auth A] Focus chain Z [auth B] Interactions & Density Focus chain AA [auth B] Focus chain BA [auth B] Focus chain CA [auth B] Focus chain DA [auth B] Focus chain GA [auth C] Focus chain HA [auth C] Focus chain IA [auth C] Focus chain JA [auth C] Focus chain MA [auth D] Focus chain NA [auth D] Focus chain OA [auth D] Focus chain PA [auth D] Focus chain S [auth A] Focus chain T [auth A] Focus chain U [auth A] Focus chain V [auth A] Focus chain W [auth A] Focus chain Z [auth B]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.00 ?
R-Value Free: 0.234
R-Value Work: 0.188
R-Value Observed: 0.190
Space Group: P 1 2₁ 1

Unit Cell:

Length ( ? )	Angle ( ? )
a = 86.66	α = 90
b = 141.12	β = 90.59
c = 169.53	γ = 90

Software Package:

Software Name	Purpose
MOLREP	phasing
REFMAC	refinement
MOSFLM	data reduction
SCALA	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2015-01-14

Deposition Author(s):

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
Version 2.1: 2024-10-30
Changes: Data collection, Database references, Structure summary

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Help and Resources

4R07

Crystal structure of human TLR8 in complex with ORN06

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

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Glycosylation

Sequence Annotations

Expand

Entity ID: 2

Glycosylation Resources

Entity ID: 3

Glycosylation Resources

Entity ID: 4

Glycosylation Resources

Entity ID: 5

Glycosylation Resources

Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)