Approaches to the analysis of structure/function of novel membrane receptors: A functional dissection of platelet GP Ib-IX-V

The glycoprotein (GP) Ib-IX-V complex is a unique receptor that in binding von Willebrand factor (vWf) initiates platelet adhesion in haemostasis and thrombosis. The lack of homology with other receptor systems, particularly in the ligand-binding domain, as well as the lack of consensus signaling motifs within the cytoplasmic domain, has hindered progress in understanding the structure and function of this important receptor. This review focuses on approaches that have been employed to define the functional role of this receptor, and the mechanism by which it signals platelet activation. These include exploiting species differences in receptor-ligand recognition, structural and functional comparisons with other receptor-ligand systems, and more classical biochemical and sequence comparison approaches.