Characterization of a TIR-like protein from Paracoccus denitrificans.
Based on protein sequence homology searches, we found a conserved open reading frame within the genome of several human pathogenic bacteria showing a resemblance to the mammalian TIR domain. We cloned, expressed, and characterized the corresponding gene product from Paracoccus denitrificans using several biophysical techniques. The protein consists of two independently folded domains. As predicted from the amino acid sequence and experimentally confirmed here, the N-terminal domain consists of a alpha-helical coiled-coil. The NMR data indicates that the C-terminal TIR-like domain folds into a compact protein. Finally, using GST pull-down experiments, we show that the bacteria TIR-like domain binds to the mammalian receptor (TLR4) and adaptor (MyD88) TIR domains. We postulate that prokaryotic pathogens utilize the TIR-like proteins to interfere with the innate immune response of the mammalian host so that the bacterial infection can progress undetected.
Low
Lieh Yoon
LY
Center for Inflammation and Infectious Diseases, La Jolla, CA 92037, USA.
Mukasa
Takashi
T
Reed
John C
JC
Pascual
Jaime
J
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D010231:Paracoccus denitrificans / Q000737:chemistry*; D010447:Peptide Hydrolases / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D051193:Toll-Like Receptors / Q000737:chemistry*
D051193:Toll-Like Receptors; D010447:Peptide Hydrolases