title: Structure of human urokinase plasminogen activator in complex with its receptor.
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.
authors.affiliation: Division of Hemostasis and Thrombosis, Center for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Huai
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Mazar
authors.forename: Alice
authors.initials: A
authors.lastname: Kuo
authors.forename: Graham C
authors.initials: GC
authors.lastname: Parry
authors.forename: David E
authors.initials: DE
authors.lastname: Shaw
authors.forename: Jennifer
authors.initials: J
authors.lastname: Callahan
authors.forename: Yongdong
authors.initials: Y
authors.lastname: Li
authors.forename: Cai
authors.initials: C
authors.lastname: Yuan
authors.forename: Chuanbing
authors.initials: C
authors.lastname: Bian
authors.forename: Liqing
authors.initials: L
authors.lastname: Chen
authors.forename: Bruce
authors.initials: B
authors.lastname: Furie
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Furie
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Cines
authors.forename: Mingdong
authors.initials: M
authors.lastname: Huang
mesh_terms: D000906:Antibodies / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000906:Antibodies; D008024:Ligands; C524898:PLAUR protein, human; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator