Heterogeneity of plasma von willebrand factor multimers resulting from proteolysis of the constituent subunit

J. A. Dent, M. Galbusera, Z. M. Ruggeri

Research output: Contribution to journalArticle

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Abstract

In this report we demonstrate that proteolytic cleavage of the constituent subunit is one of the causes determining the heterogeneous size distribution of plasma von Willebrand factor (vWf) multimers. As shown by two-dimensional nonreduced/reduced agarose/polyacrylamide gel electrophoresis, the structure of circulating vWf molecules may deviate from that represented by assemblage of a variable number of identical subunits. Indeed, even though the largest multimers in normal plasma appear to be composed predominantly of intact 225-kD subunits, those of intermediate and smaller size contain also 189-, 176-, and 140-kD proteolytic fragments. Different subunit composition patterns are repeated regularly in multimers of increasing molecular mass, yielding series of bands with similar structure. One of these series consists of molecules without evidence of proteolytic fragmentation, and its smallest member appears to be a dimer of 225-kD subunits. Type IIA von Willebrand disease, characterized by absence of the largest multimers, displays a pattern wherein the fragments of 176 and 140 kD are relatively increased, that of 189 kD is markedly decreased or absent, but the composition of individual multimers is otherwise similar to that of species seen also in normal plasma. In contrast to those in the circulation, all normal platelet vWf multimers contain only intact subunit. These results suggest that proteolytic cleavage of plasma vWf subunits occurs after release from cellular sites, whereas platelet vWf stored in α-granules is protected from proteolysis. These findings provide information that may be relevant for understanding the normal processing of vWf multimers and for elucidating the pathogenesis of some of the congenital and acquired structural abnormalities of this molecule.

Original languageEnglish
Pages (from-to)774-782
Number of pages9
JournalJournal of Clinical Investigation
Volume88
Issue number3
Publication statusPublished - 1991

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von Willebrand Factor
Proteolysis
Blood Platelets
Type 2 von Willebrand Disease
Agar Gel Electrophoresis
Polyacrylamide Gel Electrophoresis

Keywords

  • Adhesive protein
  • Platelets
  • Satellite band
  • Two-dimensional gel electrophoresis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Heterogeneity of plasma von willebrand factor multimers resulting from proteolysis of the constituent subunit. / Dent, J. A.; Galbusera, M.; Ruggeri, Z. M.

In: Journal of Clinical Investigation, Vol. 88, No. 3, 1991, p. 774-782.

Research output: Contribution to journalArticle

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