| RRC ID |
45884
|
| Author |
Wohlschlager T, Butschi A, Grassi P, Sutov G, Gauss R, Hauck D, Schmieder SS, Knobel M, Titz A, Dell A, Haslam SM, Hengartner MO, Aebi M, Künzler M.
|
| Title |
Methylated glycans as conserved targets of animal and fungal innate defense.
|
| Journal |
Proc Natl Acad Sci U S A
|
| Abstract |
Effector proteins of innate immune systems recognize specific non-self epitopes. Tectonins are a family of β-propeller lectins conserved from bacteria to mammals that have been shown to bind bacterial lipopolysaccharide (LPS). We present experimental evidence that two Tectonins of fungal and animal origin have a specificity for O-methylated glycans. We show that Tectonin 2 of the mushroom Laccaria bicolor (Lb-Tec2) agglutinates Gram-negative bacteria and exerts toxicity toward the model nematode Caenorhabditis elegans, suggesting a role in fungal defense against bacteria and nematodes. Biochemical and genetic analysis of these interactions revealed that both bacterial agglutination and nematotoxicity of Lb-Tec2 depend on the recognition of methylated glycans, namely O-methylated mannose and fucose residues, as part of bacterial LPS and nematode cell-surface glycans. In addition, a C. elegans gene, termed samt-1, coding for a candidate membrane transport protein for the presumptive donor substrate of glycan methylation, S-adenosyl-methionine, from the cytoplasm to the Golgi was identified. Intriguingly, limulus lectin L6, a structurally related antibacterial protein of the Japanese horseshoe crab Tachypleus tridentatus, showed properties identical to the mushroom lectin. These results suggest that O-methylated glycans constitute a conserved target of the fungal and animal innate immune system. The broad phylogenetic distribution of O-methylated glycans increases the spectrum of potential antagonists recognized by Tectonins, rendering this conserved protein family a universal defense armor.
|
| Volume |
111(27)
|
| Pages |
E2787-96
|
| Published |
2014-7-8
|
| DOI |
10.1073/pnas.1401176111
|
| PII |
1401176111
|
| PMID |
24879441
|
| PMC |
PMC4103367
|
| MeSH |
Agaricales / immunology*
Amino Acid Sequence
Animals
Caenorhabditis elegans / immunology
Horseshoe Crabs / immunology
Immunity, Innate*
Membrane Proteins / chemistry
Membrane Proteins / metabolism
Methylation
Molecular Sequence Data
Phylogeny
Polysaccharides / metabolism*
Sequence Homology, Amino Acid
|
| IF |
9.412
|
| Times Cited |
39
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| C.elegans |
tm1078
tm2725
tm2530 |
