Soluble human TLR2 ectodomain binds diacylglycerol from microbial lipopeptides and glycolipids

Maximiliano J. Jiménez-Dalmaroni, Catherine M. Radcliffe, David J. Harvey, Mark R. Wormald, Petra Verdino, Gary D. Ainge, David S. Larsen, Gavin F. Painter, Richard Ulevitch, Bruce Beutler, Pauline M. Rudd, Raymond A. Dwek, Ian A. Wilson

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

TLRs are key innate immune receptors that recognize conserved features of biological molecules that are found in microbes. In particular, TLR2 has been reported to be activated by different kinds of microbial ligands. To advance our understanding of the interaction of TLR2 with its ligands, the recombinant human TLR2 ectodomain (hTLR2ED) was expressed using a baculovirus/insect cell expression system and its biochemical, as well as ligand binding, properties were investigated. The hTLR2ED binds synthetic bacterial and mycoplasmal lipopeptides, lipoteichoic acid from Staphylococcus aureus, and synthetic lipoarabinomannan precursors from Mycobacterium at extracellular physiological conditions, in the absence of its co-receptors TLR1 and TLR6. We also determined that lipopeptides and glycolipids cannot bind simultaneously to hTLR2ED and that the phosphatidyl inositol mannoside 2 (Pim2) is the minimal lipoarabinomannan structure for binding to hTLR2ED. Binding of hTLR2ED to Pim4, which contains a diacylglycerol group with one of its acyl chains containing 19 carbon atoms, indicates that hTLR2ED can bind ligands with acyl chains longer than 16 carbon atoms. In summary, our data indicate that diacylglycerol is the ligand moiety of microbial glycolipids and lipoproteins that bind to hTLR2ED and that both types of ligands bind to the same binding site of hTLR2ED.

Original languageEnglish (US)
Pages (from-to)175-193
Number of pages19
JournalInnate Immunity
Volume21
Issue number2
DOIs
StatePublished - Feb 8 2015

Fingerprint

Lipopeptides
Glycolipids
Diglycerides
Ligands
Toll-Like Receptor 6
Carbon
Toll-Like Receptor 1
Baculoviridae
Mycobacterium
Lipoproteins
Insects
Staphylococcus aureus
Binding Sites

Keywords

  • Diacylglycerol ligands
  • FSL-1
  • lipoarabinomannan
  • lipoteichoic acid
  • TLR2

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Immunology
  • Microbiology
  • Infectious Diseases

Cite this

Jiménez-Dalmaroni, M. J., Radcliffe, C. M., Harvey, D. J., Wormald, M. R., Verdino, P., Ainge, G. D., ... Wilson, I. A. (2015). Soluble human TLR2 ectodomain binds diacylglycerol from microbial lipopeptides and glycolipids. Innate Immunity, 21(2), 175-193. https://doi.org/10.1177/1753425914524077

Soluble human TLR2 ectodomain binds diacylglycerol from microbial lipopeptides and glycolipids. / Jiménez-Dalmaroni, Maximiliano J.; Radcliffe, Catherine M.; Harvey, David J.; Wormald, Mark R.; Verdino, Petra; Ainge, Gary D.; Larsen, David S.; Painter, Gavin F.; Ulevitch, Richard; Beutler, Bruce; Rudd, Pauline M.; Dwek, Raymond A.; Wilson, Ian A.

In: Innate Immunity, Vol. 21, No. 2, 08.02.2015, p. 175-193.

Research output: Contribution to journalArticle

Jiménez-Dalmaroni, MJ, Radcliffe, CM, Harvey, DJ, Wormald, MR, Verdino, P, Ainge, GD, Larsen, DS, Painter, GF, Ulevitch, R, Beutler, B, Rudd, PM, Dwek, RA & Wilson, IA 2015, 'Soluble human TLR2 ectodomain binds diacylglycerol from microbial lipopeptides and glycolipids', Innate Immunity, vol. 21, no. 2, pp. 175-193. https://doi.org/10.1177/1753425914524077
Jiménez-Dalmaroni MJ, Radcliffe CM, Harvey DJ, Wormald MR, Verdino P, Ainge GD et al. Soluble human TLR2 ectodomain binds diacylglycerol from microbial lipopeptides and glycolipids. Innate Immunity. 2015 Feb 8;21(2):175-193. https://doi.org/10.1177/1753425914524077
Jiménez-Dalmaroni, Maximiliano J. ; Radcliffe, Catherine M. ; Harvey, David J. ; Wormald, Mark R. ; Verdino, Petra ; Ainge, Gary D. ; Larsen, David S. ; Painter, Gavin F. ; Ulevitch, Richard ; Beutler, Bruce ; Rudd, Pauline M. ; Dwek, Raymond A. ; Wilson, Ian A. / Soluble human TLR2 ectodomain binds diacylglycerol from microbial lipopeptides and glycolipids. In: Innate Immunity. 2015 ; Vol. 21, No. 2. pp. 175-193.
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