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

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-pha...

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Bibliographic Details
Published in:Biochemistry (Easton) 2004-03, Vol.43 (11), p.2996-3007
Main Authors: Müthing, Johannes, Meisen, Iris, Bulau, Patrick, Langer, Martin, Witthohn, Klaus, Lentzen, Hans, Neumann, Ulrich, Peter-Katalinić, Jasna
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi0301892