title: In silico docking of urokinase plasminogen activator and integrins.
abstract: BACKGROUND
  Urokinase, its receptor and the integrins are functionally associated and involved in regulation of cell signaling, migration, adhesion and proliferation. No structural information is available on this potential multimolecular complex. However, the tri-dimensional structure of urokinase, urokinase receptor and integrins is known.
  
  
  RESULTS
  We have modeled the interaction of urokinase on two integrins, alphaIIbbeta3 in the open configuration and alphavbeta3 in the closed configuration. We have found that multiple lowest energy solutions point to an interaction of the kringle domain of uPA at the boundary between alpha and beta chains on the surface of the integrins. This region is not far away from peptides that have been previously shown to have a biological role in urokinase receptor/integrins dependent signaling.
  
  
  CONCLUSIONS
  We demonstrated that in silico docking experiments can be successfully carried out to identify the binding mode of the kringle domain of urokinase on the scaffold of integrins in the open and closed conformation. Importantly we found that the binding mode was the same on different integrins and in both configurations. To get a molecular view of the system is a prerequisite to unravel the complex protein-protein interactions underlying urokinase/urokinase receptor/integrin mediated cell motility, adhesion and proliferation and to design rational in vitro experiments.
authors.affiliation: San Raffaele Scientific Institute, Milan, Italy. bernard_degryse@yahoo.fr
authors.forename: Bernard
authors.initials: B
authors.lastname: Degryse
authors.forename: Juan
authors.initials: J
authors.lastname: Fernandez-Recio
authors.forename: Valentina
authors.initials: V
authors.lastname: Citro
authors.forename: Francescol
authors.initials: F
authors.lastname: Blasi
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Cubellis
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D016023:Integrins / Q000737:chemistry* / Q000648:ultrastructure*; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods*; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry* / Q000648:ultrastructure*
chemical_list: D016023:Integrins; D014568:Urokinase-Type Plasminogen Activator