VWF self-association: more bands for the buck.

摘要

The hemostatic function of von Wille-brand factor (VWF) depends on its degree of multimerization, which results from posttranslational assembly of the nascent VWF chains in the endoplasmic reticulum and Golgi apparatus. Intracellular assembly is promoted by the VWF propeptide, a 741-amino acid sequence at the N-terminus of the nascent VWF polypeptide that acts as a disulfide isomerase to promote the formation of unique disulfide bonds between VWF dimers to form an array of VWF mul-timers that are stored in endothelial Weibel-Palade bodies or platelet alpha-granules. These newly synthesized multimers can be extremely large (ultra-large VWF [ULVWF]) and hyperadhesive. Upon their secretion into the blood and under shear stress, ULVWF multimers are proteolytically cleaved by the plasma metalloprotease