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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies / chemistry
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Antibodies / metabolism
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Crystallography, X-Ray
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Humans
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Hydrogen Bonding
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Hydrophobic and Hydrophilic Interactions
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Ligands
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Models, Molecular
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism
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Protein Binding
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Protein Conformation
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Receptors, Cell Surface / chemistry*
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Receptors, Cell Surface / immunology
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Receptors, Cell Surface / metabolism
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Receptors, Urokinase Plasminogen Activator
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Urokinase-Type Plasminogen Activator / chemistry*
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Urokinase-Type Plasminogen Activator / metabolism
Substances
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Antibodies
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Ligands
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PLAUR protein, human
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Peptide Fragments
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Receptors, Cell Surface
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Receptors, Urokinase Plasminogen Activator
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Urokinase-Type Plasminogen Activator