1YWH

crystal structure of urokinase plasminogen activator receptor

Summary for 1YWH

• Entry DOI: 10.2210/pdb1ywh/pdb
• Descriptor: Urokinase plasminogen activator surface receptor, antagonist peptide, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: upar, three-finger fold, protein-peptide complex, hydrolase receptor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 16
• Total formula weight: 304707.61

Authors

Llinas, P.,Le Du, M.H.,Gardsvoll, H.,Dano, K.,Ploug, M.,Gilquin, B.,Stura, E.A.,Menez, A. (deposition date: 2005-02-18, release date: 2005-05-10, Last modification date: 2024-10-30)

Primary citation

Llinas, P.,Le Du, M.H.,Gardsvoll, H.,Dano, K.,Ploug, M.,Gilquin, B.,Stura, E.A.,Menez, A.
Crystal structure of the human urokinase plasminogen activator receptor bound to an antagonist peptide
EMBO J., 24:1655-1663, 2005

PubMed Abstract: 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.

PubMed: 15861141
DOI: 10.1038/sj.emboj.7600635

Experimental method

X-RAY DIFFRACTION (2.7 Å)