title: Methylated glycans as conserved targets of animal and fungal innate defense.
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.
authors.affiliation: Institute of Microbiology, Swiss Federal Institute of Technology (ETH) Zürich, 8093 Zürich, Switzerland;
authors.forename: Therese
authors.initials: T
authors.lastname: Wohlschlager
authors.affiliation: Institute of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland;
authors.forename: Alex
authors.initials: A
authors.lastname: Butschi
authors.affiliation: Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom;
authors.forename: Paola
authors.initials: P
authors.lastname: Grassi
authors.affiliation: Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom;
authors.forename: Grigorij
authors.initials: G
authors.lastname: Sutov
authors.affiliation: Institute of Microbiology, Swiss Federal Institute of Technology (ETH) Zürich, 8093 Zürich, Switzerland;
authors.forename: Robert
authors.initials: R
authors.lastname: Gauss
authors.affiliation: Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany; andChemical Biology of Carbohydrates, Helmholtz Institute for Pharmaceutical Research Saarland, 66123 Saarbrücken, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Hauck
authors.affiliation: Institute of Microbiology, Swiss Federal Institute of Technology (ETH) Zürich, 8093 Zürich, Switzerland;
authors.forename: Stefanie S
authors.initials: SS
authors.lastname: Schmieder
authors.affiliation: Institute of Microbiology, Swiss Federal Institute of Technology (ETH) Zürich, 8093 Zürich, Switzerland;
authors.forename: Martin
authors.initials: M
authors.lastname: Knobel
authors.affiliation: Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany; andChemical Biology of Carbohydrates, Helmholtz Institute for Pharmaceutical Research Saarland, 66123 Saarbrücken, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Titz
authors.affiliation: Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom;
authors.forename: Anne
authors.initials: A
authors.lastname: Dell
authors.affiliation: Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom;
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Haslam
authors.affiliation: Institute of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland;
authors.forename: Michael O
authors.initials: MO
authors.lastname: Hengartner
authors.affiliation: Institute of Microbiology, Swiss Federal Institute of Technology (ETH) Zürich, 8093 Zürich, Switzerland;
authors.forename: Markus
authors.initials: M
authors.lastname: Aebi
authors.affiliation: Institute of Microbiology, Swiss Federal Institute of Technology (ETH) Zürich, 8093 Zürich, Switzerland; mkuenzle@ethz.ch.
authors.forename: Markus
authors.initials: M
authors.lastname: Künzler
mesh_terms: D000363:Agaricales / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000276:immunology; D006737:Horseshoe Crabs / Q000276:immunology; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008745:Methylation; D008969:Molecular Sequence Data; D010802:Phylogeny; D011134:Polysaccharides / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D008565:Membrane Proteins; D011134:Polysaccharides