Methylated glycans as conserved targets of animal and fungal innate defense

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 27; pp. E2787 - E2796
• Main Authors: Wohlschlager, Therese, Butschi, Alex, Grassi, Paola, Sutov, Grigorij, Gauss, Robert, Hauck, Dirk, Schmieder, Stefanie S, Knobel, Martin, Titz, Alexander, Dell, Anne, Haslam, Stuart M, Hengartner, Michael O, Aebi, Markus, Künzler, Markus
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 08.07.2014; National Acad Sciences
• Series: PNAS Plus
• Subjects: Agaricales - immunology; Amino Acid Sequence; Animals; Biological Sciences; Caenorhabditis elegans; Caenorhabditis elegans - immunology; Cytoplasm; Decapoda; Fungi; Gram-negative bacteria; Horseshoe Crabs - immunology; Immunity, Innate; Laccaria bicolor; Limulus; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Methylation; Molecular Sequence Data; Nematoda; Nematodes; Phylogeny; PNAS Plus; Polysaccharides - metabolism; Proteins; Sequence Homology, Amino Acid; Substrates; Tachypleus tridentatus; Toxicity
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1401176111

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.