Crystal structure of the human urokinase plasminogen activator receptor bound to an antagonist peptide
| Autor: | Paola Llinas, Keld Danø, Henrik Gårdsvoll, André Ménez, Michael Ploug, Enrico A. Stura, Bernard Gilquin, Marie Hélène Le Du |
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| Rok vydání: | 2005 |
| Předmět: |
Integrin
Molecular Conformation Receptors Cell Surface Peptide Plasma protein binding Article General Biochemistry Genetics and Molecular Biology Receptors Urokinase Plasminogen Activator Protein–protein interaction Humans Receptor Molecular Biology chemistry.chemical_classification General Immunology and Microbiology biology General Neuroscience Urokinase-Type Plasminogen Activator Molecular biology Recombinant Proteins Cell biology Urokinase receptor chemistry biology.protein Vitronectin Crystallization Peptides Plasminogen activator Protein Binding |
| Zdroj: | The EMBO Journal. 24:1655-1663 |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.1038/sj.emboj.7600635 |
| Popis: | We report the crystal structure of a soluble form of human urokinase-type 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 (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. |
| Databáze: | OpenAIRE |
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