Independent assembly and secretion of a dimeric adhesive domain of von Willebrand factor containing the glycoprotein Ib-binding site

von Willebrand factor (vWF) is a multimeric glycoprotein that supports platelet adhesion on thrombogenic surfaces as part of the normal hemostatic response to vascular injury. We have employed a domain-specific expression strategy to analyze the biosynthetic processing steps and minimum structural r...

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Bibliographic Details
Published in:The Journal of biological chemistry 1991-07, Vol.266 (19), p.12342-12347
Main Authors: AZUMA, H, DENT, J. A, SUGIMOTO, M, RUGGERI, Z. M, WARE, J
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Binding Sites
Biological and medical sciences
Blood coagulation. Blood cells
Cell Line
Chromatography, Affinity
Coagulation factors
Collagen - antagonists & inhibitors
Cricetinae
DNA - genetics
Fundamental and applied biological sciences. Psychology
Glycosylation
Haplorhini
Heparin Antagonists - metabolism
Molecular and cellular biology
Molecular Sequence Data
Plasmids
Platelet Aggregation
Platelet Membrane Glycoproteins - antagonists & inhibitors
Platelet Membrane Glycoproteins - metabolism
Protein Processing, Post-Translational
Transformation, Genetic
Tunicamycin - pharmacology
von Willebrand Factor - genetics
von Willebrand Factor - metabolism
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Summary:von Willebrand factor (vWF) is a multimeric glycoprotein that supports platelet adhesion on thrombogenic surfaces as part of the normal hemostatic response to vascular injury. We have employed a domain-specific expression strategy to analyze the biosynthetic processing steps and minimum structural requirements for assembly of the platelet receptor glycoprotein Ib-binding domain of vWF. A chimeric cDNA that codes for the vWF signal peptide and a segment of vWF internal primary sequence, residues 441-730, directs the secretion of a functional vWF fragment from mammalian cells. The recombinant molecule intrinsically assembles through intermolecular disulfide bond formation into a dimeric adhesive domain without contributions from other regions of vWF, including propeptide, previously indicated as essential for vWF multimer assembly. Prevention of N-linked glycosylation on the recombinant domain does not impair dimer formation or the ability to support platelet aggregation. These results identify a minimum structural element for vWF subunit assembly and provide new insights into the processing steps to produce vWF multimers and adhesive domains.
ISSN:0021-9258
1083-351X
DOI:10.1016/s0021-9258(18)98902-7