O-glycan sialylation and the structure of the stalk-like region of the T cell co-receptor CD8
| Autor: | Pauline M. Rudd, Brendan J. Classon, Olga Miroshnychenko, Mark R. Wormald, Louise Royle, David Harvey, David A. Shore, Raymond A. Dwek, Simon J. Davis, Mai Vuong, Robert J.C. Gilbert, Anthony H. Merry |
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| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Models
Molecular Glycosylation Molecular model Protein Conformation CD8 Antigens Recombinant Fusion Proteins T cell Molecular Sequence Data CHO Cells In Vitro Techniques Biochemistry Mice chemistry.chemical_compound Protein structure Polysaccharides Cricetinae Carbohydrate Conformation medicine Animals Amino Acid Sequence Molecular Biology Peptide sequence Chromatography High Pressure Liquid Molecular Structure Chinese hamster ovary cell Mucin Cell Biology Rats carbohydrates (lipids) medicine.anatomical_structure Carbohydrate Sequence chemistry Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Sialic Acids Biophysics Carbohydrate conformation |
| Zdroj: | The Journal of biological chemistry. 278(29) |
| ISSN: | 1083-351X 0021-9258 |
| Popis: | Studies of mucins suggest that the structural effects of O-glycans are restricted to steric interactions between peptide-linked GalNAc residues and adjacent polypeptide residues. It has been proposed, however, that differential O-glycan sialylation alters the structure of the stalk-like region of the T cell co-receptor, CD8, and that this, in turn, modulates ligand binding (Daniels, M. A., Devine, L., Miller, J. D., Moser, J. M., Lukacher, A. E., Altman, J. D., Kavathas, P., Hogquist, K. A., and Jameson, S. C. (2001) Immunity 15, 1051-1061; Moody, A. M., Chui, D., Reche, P. A., Priatel, J. J., Marth, J. D., and Reinherz, E. L. (2001) Cell 107, 501-512). We characterize the glycosylation of soluble, chimeric forms of the alphaalpha- and alphabeta-isoforms of murine CD8 containing the O-glycosylated stalk of rat CD8alphaalpha, and we show that the stalk O-glycans are differentially sialylated in CHO K1 versus Lec3.2.8.1 cells (82 versus approximately 6%, respectively). Sedimentation analysis indicates that the Perrin functions, Pexp, which reflect overall molecular shape, are very similar (1.61 versus 1.54), whereas the sedimentation coefficients (s) of the CHO K1- and Lec3.2.8.1-derived proteins differ considerably (3.73 versus 3.13 S). The hydrodynamic properties of molecular models also strongly imply that the sialylated and non-sialylated forms of the chimera have parallel, equally highly extended stalks ( approximately 2.6 A/residue). Our analysis indicates that, as in the case of mucins, the overall structure of O-glycosylated stalk-like peptides is sialylation-independent and that the functional effects of differential CD8 O-glycan sialylation need careful interpretation. |
| Databáze: | OpenAIRE |
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