Structure of Human Urokinase Plasminogen Activator in Complex with Its Receptor
Qing Huai(Beth Israel Deaconess Medical Center), Andrew P. Mazar(Beth Israel Deaconess Medical Center), Alice A. Kuo(Beth Israel Deaconess Medical Center), Graham C. Parry(Beth Israel Deaconess Medical Center), David E. Shaw(Beth Israel Deaconess Medical Center), Jennifer Callahan(Beth Israel Deaconess Medical Center), Yongdong Li(Beth Israel Deaconess Medical Center), Cai Yuan(Beth Israel Deaconess Medical Center), Chuanbing Bian(Beth Israel Deaconess Medical Center), Liqing Chen(Beth Israel Deaconess Medical Center), Bruce Furie(Beth Israel Deaconess Medical Center), Barbara C. Furie(Beth Israel Deaconess Medical Center), Douglas B. Cines(Beth Israel Deaconess Medical Center), Mingdong Huang(Beth Israel Deaconess Medical Center)
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Abstract
The urokinase plasminogen activator binds to its cellular receptor with high affinity and initiates signaling cascades that are implicated in pathological processes including tumor growth, metastasis, and inflammation. We report the crystal structure at 1.9 angstroms of the urokinase receptor complexed with the urokinase amino-terminal fragment and an antibody against the receptor. The three domains of urokinase receptor form a concave shape with a central cone-shaped cavity where the urokinase fragment inserts. The structure provides insight into the flexibility of the urokinase receptor that enables its interaction with a wide variety of ligands and a basis for the design of urokinase-urokinase receptor antagonists.