In silico docking of urokinase plasminogen activator and integrins

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, IIb3 in the open configuration and v3 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 and 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 ...

• Type: Journal
• Year: 2008
• Where: BMCBI
• Authors: Bernard Degryse, Juan Fernández-Recio, Valentina Citro, Francescol Blasi, Maria Vittoria Cubellis
• Keywords: BMCBI 2008, Integrins, Kringle Domain, Urokinase