O-linked carbohydrate of recombinant von Willebrand factor influences ristocetin-induced binding to platelet glycoprotein 1b
| Autor: | Josephine A. Carew, S M Quinn, J H Stoddart, Dennis C. Lynch |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1992 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Glycosylation Platelet Aggregation Macromolecular Substances Molecular Sequence Data Platelet Membrane Glycoproteins In Vitro Techniques Platelet membrane glycoprotein chemistry.chemical_compound Structure-Activity Relationship Von Willebrand factor hemic and lymphatic diseases von Willebrand Factor Von Willebrand disease medicine Humans Platelet Amino Acid Sequence Ristocetin Glycoproteins chemistry.chemical_classification biology Heparin Binding protein Chinese hamster ovary cell General Medicine medicine.disease Molecular biology Recombinant Proteins Biochemistry chemistry biology.protein Collagen Glycoprotein circulatory and respiratory physiology Research Article Protein Binding |
| Popis: | By transfecting the full-length cDNA for human von Willebrand factor (vWf) into a line of Chinese hamster ovary cells with a defect in carbohydrate metabolism, we have prepared recombinant vWf specifically lacking O-linked carbohydrates. We have compared this under-glycosylated protein to fully glycosylated recombinant vWf with respect to several structural and binding properties. vWf deficient in O-linked glycans was synthesized, assembled into multimers, and secreted in an apparently normal manner and was not prone to degradation in the extracellular milieu. It did not differ from fully glycosylated vWf in ability to bind to heparin or to collagen type I but did interact less well with glycoprotein 1b on formalin-fixed platelets. This decreased interaction was evidenced in both a lessened overall binding to platelets and in diminished capacity to promote platelet agglutination, in the presence of ristocetin. In contrast, no difference was seen in platelet binding in the presence of botrocetin. These data indicate a possible role for O-linked carbohydrates in the vWf-glycoprotein 1b interaction promoted by ristocetin and suggest that abnormalities in carbohydrate modification might contribute to the altered ristocetin-dependent reactivity between vWf and platelets described for some variant forms of von Willebrand disease. |
| Databáze: | OpenAIRE |
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