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

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