Structural insights into the extra cellular segment of integrin beta 5 and molecular interaction studies

作者:Setti Aravind; Sankati Harsha Sagar; Devi T A Phazna; Sekhar A Chandra; Rao J Venkateshwar; Pawar Smita C*
来源:Journal of Receptors and Signal Transduction, 2013, 33(5): 319-324.
DOI:10.3109/10799893.2013.822892

摘要

Primary tumor cells often spread to other organs by metastasis. Despite of it, primary tumor cells break their surrounding extra cellular matrix (ECM) proteins and reach the destination organ by the process of intravasation and extravasation. Metastasized tumor cells induce the process of angiogenesis, this highly regulated process involves several ECM proteins. However, integrins are primarily involved in the blood vessel growth and repair. Therefore, integrins are promising angiogenesis targets. Integrins are receptors on cell surface, involved in signal transduction and attachments in extra cellular matrix (ECM). Integrin alpha V beta 3 and alpha V beta 5 are implicated in tumor angiogenesis, metastasis, inflammation and bone resorption. The crystal structure of integrin alpha v beta 5 is not available in protein structural databases, therefore; molecular model of integrin beta 5 structure was prepared and stereo chemical model quality was checked. Integrin beta 5 active sites were identified based on insilico analysis tools. Further, molecular level interactions between integrin beta 5 and ECM proteins were predicted. In the present study ECM proteins such as focal adhesion kinase 1 (FAK1), annexin A5 and P21 activated kinase 4 (PAK4) were considered for protein-protein docking, to understand inter molecular interactions. The predicted model is conceived to be stereo chemically good and can be used for molecular interaction studies of angiogenic inhibitors.

  • 出版日期2013-10

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