lebrand Factor Precursor 
GPIb 
Botrocetin 
Heparin Heparin 
Collagen Factor VIZI Sulfatide Collagen GPIIb-IIIa 
488 
474 471 4G4 463 
Top: Structure-function relationships of von Willebrand factor. 
The factor precursor comprises four types of homologous do- 
mains (A-D), repeated two to five times each. The mature sub- 
unit consists of 2, 050 amino acids. Binding sites are indicated 
for collagen, heparin, factor VIII, platelet glycoprotein lb, bo- 
trocetin, sulfatide, and platelet glycoprotein Ilb-IIIa. The loca- 
tions of two Arg-Gly- Asp- containing sequences, RGD and 
RGBS, are indicated. 
Bottom: Mutations, indicated by brackets, in exon 28 of the 
gene encoding von Willebrand factor cause von Willebrand 
disease types IIA and IIB. The segment of the factor shown in- 
cludes amino acid residues 463-921, designated by single- 
letter code. The positions of repeated domains D3 and A 1-3 are 
indicated. The green zigzag segments from Cys474 to Pro488 
and Cys695 to Pro708 indicate regions proposed to interact 
directly with platelet glycoprotein lb. One proposed type IIA 
mutation (Val551 Phe, orange circle) occurs in the region 
of the type IIB mutations. 
From Sadler, f.E. 1991. J Biol Chem 266:22777-22780. 
