PMID- 19535337
OWN - NLM
STAT- MEDLINE
DCOM- 20090928
LR  - 20211020
IS  - 0021-9258 (Print)
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Linking)
VI  - 284
IP  - 32
DP  - 2009 Aug 7
TI  - Molecular mimicry in innate immunity: crystal structure of a bacterial TIR 
      domain.
PG  - 21386-92
LID - 10.1074/jbc.C109.007591 [doi]
AB  - Macrophages detect pathogen infection via the activation of their plasma 
      membrane-bound Toll-like receptor proteins (TLRs). The heterotypic interaction 
      between the Toll/interleukin-1 receptor (TIR) domains of TLRs and adaptor 
      proteins, like Myeloid differentiation primary response gene 88 (MyD88), is the 
      first intracellular step in the signaling pathway of the mammalian innate immune 
      response. The hetero-oligomerization of the TIRs of the receptor and adaptor 
      brings about the activation of the transcription factor NF-kappaB, which 
      regulates the synthesis of pro-inflammatory cytokines. Here, we report the first 
      crystal structure of a bacterial TIR domain solved at 2.5 A resolution. The 
      three-dimensional fold of Paracoccus denitrificans TIR is identical to that 
      observed for the TIR of human TLRs and MyD88 proteins. The structure shows a 
      unique dimerization interface involving the DD-loop and EE-loop residues, whereas 
      leaving the BB-loop highly exposed. Peptide amide hydrogen-deuterium exchange 
      mass spectrometry also reveals that the same region is used for dimerization in 
      solution and in the context of the full-length protein. These results, together 
      with a functional interaction between P. denitrificans TIR and MyD88 visualized 
      in a co-immunoprecipitation assay, further substantiate the model that bacterial 
      TIR proteins adopt structural mimicry of the host active receptor TIR domains to 
      interfere with the signaling of TLRs and their adaptors to decrease the 
      inflammatory response.
FAU - Chan, Siew Leong
AU  - Chan SL
AD  - Inflammation and Infectious Diseases Center and Cancer Center, Burnham Institute 
      for Medical Research, La Jolla, California 92037, USA.
FAU - Low, Lieh Yoon
AU  - Low LY
FAU - Hsu, Simon
AU  - Hsu S
FAU - Li, Sheng
AU  - Li S
FAU - Liu, Tong
AU  - Liu T
FAU - Santelli, Eugenio
AU  - Santelli E
FAU - Le Negrate, Gaelle
AU  - Le Negrate G
FAU - Reed, John C
AU  - Reed JC
FAU - Woods, Virgil L Jr
AU  - Woods VL Jr
FAU - Pascual, Jaime
AU  - Pascual J
LA  - eng
GR  - R21 CA118595/CA/NCI NIH HHS/United States
GR  - R21 AI065602/AI/NIAID NIH HHS/United States
GR  - CA099835/CA/NCI NIH HHS/United States
GR  - R21AI065602/AI/NIAID NIH HHS/United States
GR  - R21 AI076961/AI/NIAID NIH HHS/United States
GR  - P01AI055789/AI/NIAID NIH HHS/United States
GR  - P01 AI055789/AI/NIAID NIH HHS/United States
GR  - R33 CA099835/CA/NCI NIH HHS/United States
GR  - AI076961/AI/NIAID NIH HHS/United States
GR  - CA118595/CA/NCI NIH HHS/United States
GR  - R21 CA099835/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090617
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Bacterial Proteins)
RN  - 0 (Cytokines)
RN  - 0 (MYD88 protein, human)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Bacterial Proteins/*chemistry
MH  - Crystallography, X-Ray/methods
MH  - Cytokines/metabolism
MH  - Dimerization
MH  - Escherichia coli/*metabolism
MH  - Humans
MH  - Immunoprecipitation
MH  - Inflammation
MH  - Models, Biological
MH  - Models, Molecular
MH  - Molecular Conformation
MH  - Myeloid Differentiation Factor 88/chemistry/*physiology
MH  - Paracoccus denitrificans/*metabolism
MH  - Protein Structure, Tertiary
MH  - Toll-Like Receptors/chemistry
PMC - PMC2755863
EDAT- 2009/06/19 09:00
MHDA- 2009/09/29 06:00
PMCR- 2010/08/07
CRDT- 2009/06/19 09:00
PHST- 2009/06/19 09:00 [entrez]
PHST- 2009/06/19 09:00 [pubmed]
PHST- 2009/09/29 06:00 [medline]
PHST- 2010/08/07 00:00 [pmc-release]
AID - S0021-9258(18)49491-4 [pii]
AID - C109.007591 [pii]
AID - 10.1074/jbc.C109.007591 [doi]
PST - ppublish
SO  - J Biol Chem. 2009 Aug 7;284(32):21386-92. doi: 10.1074/jbc.C109.007591. Epub 2009 
      Jun 17.