Title : Site-specific characterization of the N-linked glycans of murine prion
protein by high-performance liquid chromatography/electrospray mass spectrometry and exoglycosidase digestions
Abstract :
- The murine prion protein PrP gene encodes a protein of 254 amino acids with two consensus sites for Asn-linked glycosylation at codons 180 and 196
- A partial site-specific study of the N-linked glycans from hamster PrP has previously been carried out by mass spectrometry [Stahl, N. , Baldwin , M. A., Teplow, D. B., Hood, L., Gibson, B. W., Burlingame, A. L., and Prusiner, S. B. (1993) Biochemistry 32, 1991-2002] and revealed that the glycosylation at Asn-181 (equivalent to mouse 180) is heterogeneous, comprising over 30 glycoforms
- The identification of the glycosylated peptide spanning Asn-197 was not reported
- Recent technical advances in electrospray mass spectrometry now provide the sensitivity to detect low femtomole quantities of glycopeptides with >5000 mass resolution and 30 ppm mass measurement [Medzihradszky, K. F., Besman, M. J., and Burlingame, A. L. (1998) Rapid Commun
- Mass Spectrom
- 12, 472-478]
- This performance coupled with stepwise exoglycosidase digestion has been employed to establish the differential nature of the structural complexity (glycoforms) of the glycans at Asn-180 and Asn-196 from a single strain infected with the ME7 strain
- Some sixty structures have been found characterized by neutral and sialylated bi-, tri-, and tetraantennary complex-type bearing outer-arm alpha(1-3)-fucosylation (the Lewisx and sialyl-Lewisx epitopes), core alpha(1,6) fucosylation, and the presence of terminal HexNAc residues
- The Lewisx trisaccharide is the major nonreducing structure at Asn-180 , and significant amounts of both Lewisx and sialyl Lewisx epitopes are observed at Asn-196
- The abundance of the Lewisx and sialyl Lewisx epitopes on murine PrPSc may indicate a role for these structures in the normal function of PrPC or the pathophysiology of PrPSc
Output (sent_index, trigger,
protein,
sugar,
site):
- 0. protein, , protein, the N-linked glycans, -
- 10. epitopes, , PrPSc, epitopes, -
- 2. PrP, , PrP, the N-linked glycans, -
- 2. glycosylation, , -, -, Asn-181
- 3. glycosylated, , -, -, Asn-197
- 4. glycopeptides, , -, -, glycopeptides
- 7. Asn-180, , -, the glycans, Asn-180 and Asn-196
- 7. Asn-196, , -, the glycans, Asn-180 and Asn-196
- 8. -fucosylation, , -, terminal HexNAc residues, -
- 8. fucosylation, , -, terminal HexNAc residues, -
- 8. sialylated, , -, neutral and sialylated bi-, -
- 9. Asn-180, , -, The Lewisx trisaccharide, Asn-180
- 9. epitopes, , -, both Lewisx and sialyl Lewisx epitopes, -
- 9. observed, , -, both Lewisx and sialyl Lewisx epitopes, Asn-196
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):
- 2. PrP, -, Asn-181
- 3. PrP, -, Asn-197
- 7. PrP, the glycans, Asn-180 and Asn-196
- 9. PrP, The Lewisx trisaccharide, Asn-180
- 9. PrP, both Lewisx and sialyl Lewisx epitopes, Asn-196