A. Inbal et al., EFFECT OF TYPE IIB VON-WILLEBRAND DISEASE MUTATION ARG(545)CYS ON PLATELET GLYCOPROTEIN IB BINDING-STUDIES WITH RECOMBINANT VON-WILLEBRAND-FACTOR, Thrombosis and haemostasis, 70(6), 1993, pp. 1058-1062
Type IIB von Willebrand disease (vWD) is characterized by a selective
loss of high molecular weight von Willebrand factor (vWF) multimers in
plasma due to their abnormally enhanced reactivity with platelets. Se
veral missense mutations in the platelet glycoprotein Ib (GPIb) bindin
g domain of vWF were recently characterized that cause type IIB vWD. T
he effect of type IIB mutation Arg(545)Cys on VWF binding to platelet
GPIb was studied using recombinant wild type (rvWFWT) and mutant rvWFR
545C expressed in COS-7 cells. In the absence of ristocetin, 50% of rv
WFR545C bound spontaneously to platelet GPIb and the binding increased
to 70% in the presence of 0.2 mg/ml ristocetin; rvWFWT did not bind s
ignificantly under either condition. Botrocetin-induced binding of rvW
FR545C was only slightly increased compared to rvWFWT. These data demo
nstrate that the Arg(545)Cys mutation increases the affinity of vWF fo
r GPIb, resulting in the characteristic gain-of-function type IIB vWD
phenotype.