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10E4 Antigen of Scrapie Lesions Contains an Unusual Nonsulfated Heparan Motif
- Source :
- Journal of Biological Chemistry. 276:12539-12545
- Publication Year :
- 2001
- Publisher :
- Elsevier BV, 2001.
-
Abstract
- The carbohydrate antigen on heparan sulfate recognized by monoclonal antibody 10E4 is uniquely codistributed with the abnormal prion protein, PrP(Sc), even in the earliest detectable brain lesions of scrapie-infected mice. Determining the chemical structure of 10E4 antigen is, therefore, an important aspect of structure elucidation of scrapie lesions, and a prerequisite for designing experiments to understand its role in scrapie pathogenesis. Toward this aim, we have examined preparations of heparan sulfate, with differing sulfate contents, for binding by 10E4 antibody. The highest antigenicity was observed in a preparation (HS-1) with the lowest sulfate content. HS-1 was partially depolymerized with heparin lyase III, and oligosaccharide fragments examined for 10E4 antigen expression by the neoglycolipid technology. An antigen-positive and two antigen-negative tetrasaccharides were isolated and examined by electrospray mass spectrometry. The antigen-positive tetrasaccharide sequence on heparan sulfate was thus deduced to contain a unique unsulfated motif that includes an N-unsubstituted glucosamine in the sequence, UA-GlcN-UA-GlcNAc. Antibody binding experiments with neoglycolipids prepared from a series of heparin/heparan sulfate disaccharides, and the trisaccharide derived from the antigen-positive tetrasaccharide after removal of the terminal hexuronic acid, show that both the penultimate glucosamine and the outer nonsulfated hexuronic acid are important for 10E4 antigenicity.
- Subjects :
- Spectrometry, Mass, Electrospray Ionization
Antigenicity
PrPSc Proteins
Molecular Sequence Data
Oligosaccharides
Disaccharides
Biochemistry
Mice
chemistry.chemical_compound
Antigen
Glucosamine
medicine
Animals
Tetrasaccharide
Antigens
Molecular Biology
Polysaccharide-Lyases
chemistry.chemical_classification
Antibodies, Monoclonal
Cell Biology
Heparan sulfate
Heparin
Oligosaccharide
Molecular biology
Peptide Fragments
Recombinant Proteins
Heparin lyase
Carbohydrate Sequence
chemistry
Binding Sites, Antibody
Heparitin Sulfate
medicine.drug
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 276
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....cef1e44d768c171a137d2881f72e2906