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Innate Immun. 2015 Feb;21(2):175-93. doi: 10.1177/1753425914524077. Epub 2014 Mar 3.

Soluble human TLR2 ectodomain binds diacylglycerol from microbial lipopeptides and glycolipids.

Author information

1
Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, UK Department of Integrative Structural and Computational Biology, and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA.
2
Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, UK.
3
Department of Integrative Structural and Computational Biology, and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA.
4
Department of Chemistry, University of Otago, Dunedin, New Zealand.
5
The Ferrier Research Institute, Victoria University Of Wellington, Gracefield Research Centre, Lower Hutt, New Zealand.
6
Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA, USA.
7
Department of Genetics, The Scripps Research Institute, La Jolla, CA, USA.
8
Department of Integrative Structural and Computational Biology, and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA wilson@scripps.edu.

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.

KEYWORDS:

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

PMID:
24591200
PMCID:
PMC4392886
DOI:
10.1177/1753425914524077
[Indexed for MEDLINE]
Free PMC Article

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