Mistletoe lectin I is a sialic acid-specific lectin with strict preference to gangliosides and glycoproteins with terminal Neu5Ac alpha 2-6Gal beta 1-4GlcNAc residues

Biochemistry. 2004 Mar 23;43(11):2996-3007. doi: 10.1021/bi0301892.


Mistletoe lectin I (ML-I) is a type II ribosome-inactivating protein, which inhibits the protein biosynthesis at the ribosomal level. ML-I is composed of a catalytically active A-chain with rRNA N-glycosidase activity and a B-chain with carbohydrate binding specificities. Using comparative solid-phase binding assays along with electrospray ionization tandem mass spectrometry, ML-I was shown to preferentially bind to terminally alpha2-6-sialylated neolacto series gangliosides from human granulocytes. IV(6)Neu5Ac-nLc4Cer, VI(6)Neu5Ac-nLc6Cer, and VIII(6)Neu5Ac-nLc8Cer were identified as ML-I receptors, whereas the isomeric alpha2-3-sialylated neolacto series gangliosides were not recognized. Only marginal binding of ML-I to terminal galactose residues of neutral glycosphingolipids with a Galbeta1-4Glc or Galbeta1-4GlcNAc sequence was determined, whereas a distal Galalpha1-4Gal, GalNAcbeta1-3Gal, or GalNAcbeta1-4Gal disaccharide did not bind at all. Among the glycoproteins investigated in Western blot and microwell adsorption assays, only those carrying Neu5Acalpha2-6Galbeta1-4GlcNAc residues, exclusively, predominantly, or even as less abundant constituents in an assembly with Neu5Acalpha2-3Galbeta1-4GlcNAc-terminated glycans, displayed high ML-I binding capacity. From our data we conclude that (i) ML-I has to be considered as a sialic acid- and not a galactose-specific lectin and (ii) neolacto series gangliosides and sialoglycoproteins with type II glycans, which share the Neu5Acalpha2-6Galbeta1-4GlcNAc terminus, are true ML-I receptors. This strict preference might help to explain the immunostimulatory potential of ML-I toward certain leukocyte subpopulations and its therapeutic success as a cytotoxic anticancer drug.

MeSH terms

  • Adsorption
  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / chemistry
  • Binding Sites, Antibody
  • Carbohydrate Sequence
  • Cattle
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Electrophoresis, Polyacrylamide Gel
  • Gangliosides / blood
  • Gangliosides / chemistry*
  • Glycosphingolipids / blood
  • Glycosphingolipids / chemistry
  • Humans
  • Lectins / chemistry*
  • Molecular Sequence Data
  • N-Acetylneuraminic Acid / blood
  • N-Acetylneuraminic Acid / chemistry
  • Nanotechnology
  • Oligosaccharides / blood
  • Oligosaccharides / chemistry*
  • Peptide Mapping
  • Plant Preparations / chemistry*
  • Plant Preparations / immunology
  • Plant Preparations / metabolism
  • Plant Proteins / chemistry*
  • Plant Proteins / immunology
  • Plant Proteins / metabolism
  • Protein Binding
  • Ribosome Inactivating Proteins, Type 2
  • Sialoglycoproteins / blood
  • Sialoglycoproteins / chemistry*
  • Spectrometry, Mass, Electrospray Ionization
  • Toxins, Biological / chemistry*
  • Toxins, Biological / immunology
  • Toxins, Biological / metabolism
  • Viscum / chemistry*


  • Antibodies, Monoclonal
  • Gangliosides
  • Glycosphingolipids
  • Lectins
  • Oligosaccharides
  • Plant Preparations
  • Plant Proteins
  • Ribosome Inactivating Proteins, Type 2
  • Sialoglycoproteins
  • Toxins, Biological
  • mistletoe lectin I
  • ribosome inactivating protein, Viscum
  • N-acetylneuraminosyl(alpha2-6)lactosamine
  • N-Acetylneuraminic Acid