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PDBsum entry 4r09

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protein ligands Protein-protein interface(s) links
Immune system PDB id
4r09

 

 

 

 

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Contents
Protein chains
749 a.a.
Ligands
NAG-NAG-BMA-MAN-
MAN
×2
NAG-NAG ×6
NAG-NAG-BMA ×3
URI ×4
06S ×4
UPT ×4
NAG ×3
PDB id:
4r09
Name: Immune system
Title: Crystal structure of human tlr8 in complex with orn06s
Structure: Toll-like receptor 8. Chain: a, b, c, d. Fragment: extracellular domain. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: tlr8, unq249/pro286. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Expression_system_cell_line: schneider 2(s2) cells.
Resolution:
2.62Å     R-factor:   0.220     R-free:   0.285
Authors: H.Tanji,U.Ohto,T.Shimizu
Key ref: H.Tanji et al. (2015). Toll-like receptor 8 senses degradation products of single-stranded RNA. Nat Struct Biol, 22, 109-115. PubMed id: 25599397 DOI: 10.1038/nsmb.2943
Date:
30-Jul-14     Release date:   14-Jan-15    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9NR97  (TLR8_HUMAN) -  Toll-like receptor 8 from Homo sapiens
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1041 a.a.
749 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1038/nsmb.2943 Nat Struct Biol 22:109-115 (2015)
PubMed id: 25599397  
 
 
Toll-like receptor 8 senses degradation products of single-stranded RNA.
H.Tanji, U.Ohto, T.Shibata, M.Taoka, Y.Yamauchi, T.Isobe, K.Miyake, T.Shimizu.
 
  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.
 

 

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