EPCR binding to this receptor appears to limit binding of neutrophils to activated endothelium, possibly providing a protective effect for the vasculature. This trafficking appears to alter the expression of a subset of genes. These properties suggested that EPCR would play a critical role in development. Replacement of wild-type EPCR in mice with specific mutations designed to block single EPCR functions is in progress to elucidate the physiological significance of each of the functions described above. A complete understanding of how the blood clotting process is regulated requires an appreciation of the structure of the proteins involved in the process, both alone and in the complexes responsible for their biological activity.
Current work seeks to obtain crystal structures of the proteins alone and in the complexes.
Mutational studies have already demonstrated that EPCR, a protein homologous to the major histocompatibility complex class 1 family of molecules, binds protein C through regions of the molecule distinct from those used by other family members for binding their respective ligands. These studies will help us understand why the formation of complexes between two proteins in the coagulation system elicits 1,000-fold or more enhancement of functions. Together, these studies should improve our understanding of the blood clotting process in health and disease. Some aspects of this work were supported by grants from the National Institutes of Health.