Crystallization of soluble urokinase receptor (suPAR) in complex with urokinase amino-terminal fragment (1-143)

Urokinase-type plasminogen activator (urokinase, uPA) and its receptor, uPAR, have been implicated in cell adhesion, migration, tissue remodelling and tumour-cell invasion. uPAR has three domains and is anchored to membranes by a glycosyl-phosphatidylinositol (GPI) anchor. Recombinant uPAR without its GPI anchor, soluble uPAR (suPAR), tends to oligomerize, making it difficult to crystallize. The amino-terminal fragment (ATF) of uPA is the major receptor-binding determinant in suPAR and binds to suPAR with nanomolar affinity, indistinguishable from membrane-bound uPAR. It is shown that uPA is capable of dissociating the oligomerization of suPAR and the crystallization of the suPAR-ATF complex is reported here. The resulting crystals diffract to 3.1 Å using a synchrotron X-ray source.