The role of the D1 domain of the von Willebrand factor propeptide in multimerization of VWF.

摘要: While studying patient plasma containing an unusual pattern of von Willebrand factor (VWF) multimers, we discovered a previously unreported phenomenon: heavy predominance dimeric VWF. Genomic analysis revealed new congenital mutation (Tyr87Ser) that altered the final stages VWF biosynthesis. This in propeptide (VWFpp) resulted synthesis with almost complete loss N-terminal multimerization. The multimer appears to result from separate alleles' synthesizing wild-type or mutant (dimeric) VWF, homodimers composing predominant protomeric species. We have expressed protein Tyr87Ser and analyzed intracellular processing resulting biological functions. displayed several specific functions: collagen binding, VIII ristocetin-induced platelet binding. However, granular storage was normal, demonstrating lack multimerization does not preclude storage. Although tertiary structure VWFpp remains unknown, amino acid is located region highly conserved across species may play major role Our data suggest one function cysteine-rich align adjacent subunits into correct configuration, serving as intramolecular chaperone. integrity essential maintain proper spacing alignment multiple cysteines N-terminus mature