Full-length von Willebrand factor (vWF) cDNA encodes a highly repetitive protein considerably larger than the mature vWF subunit

Abstract

Full-length human von Willebrand factor (vWF) cDNA was assembled from partial, overlapping vWF cDNAs. This cDNA construct includes a coding sequence of 8439 nucleotides which encode a single-chain precursor of 2813 amino-acid residues, representing a putative signal peptide, a prosequence and mature vWF of 22, 741 and 2050 amino acids, respectively. This represents the longest coding sequence determined to date. In-vitro expression of full-length vWF cDNA revealed the synthesis of a polypeptide with a mol. wt corresponding with that of the unglycosylated precursor. The precursor is a highly repetitive protein which consists of two duplicated (B, C), a triplicated (A), a quadruplicated (D) and a partly duplicated domain (D'), in the following order: H-D1-D2-D'-D3-A1-A2-A3-D4-B1-B2-C1-C2-OH. Both the prosequence, composed of two D domains (D1, D2), and mature vWF harbor an arg-gly-asp ('R-G-D') sequence which has been implicated in cell-attachment functions. It is argued that the pro-sequence is equivalent to von Willebrand Antigen II (vW AgII).