Title : Crystal structure of the human
urokinase plasminogen activator receptor bound to an antagonist
peptide
Abstract :
- We report the crystal structure of a soluble form of human urokinase-type plasminogen activator receptor plasminogen activator receptor ( uPAR / CD87 ), which is expressed at the invasive areas of the tumor-stromal microenvironment in many human cancers
- The structure was solved at 2.7 A in association with a competitive peptide inhibitor of the urokinase-type plasminogen activator plasminogen activator ( uPA )- uPAR interaction
- uPAR is composed of three consecutive three-finger domains organized in an almost circular manner, which generates both a deep internal cavity where the peptide binds in a helical conformation, and a large external surface
- This knowledge combined with the discovery of a convergent binding motif shared by the antagonist peptide and uPA allowed us to build a model of the human uPA- uPAR complex
- This model reveals that the receptor-binding module of uPA engages the uPAR central cavity, thus leaving the external receptor surface accessible for other protein interactions ( vitronectin and integrins)
- By this unique structural assembly, uPAR can orchestrate the fine interplay with the partners that are required to guide uPA-focalized proteolysis on the cell surface and control cell adhesion and migration
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