Investigating Molecular Interactions Between Epstein-Barr Virus Nuclear Antigen-1 and Partner Proteins

Hussain, M., Baillie, G. , Gatherer, D. and Wilson, J.B. (2012) Investigating Molecular Interactions Between Epstein-Barr Virus Nuclear Antigen-1 and Partner Proteins. Tenovus 30th Aniversary Symposium: Molecular Mechanisms of Disease, Glasgow, UK, 6-7 Jun 2012.

Abstract

Epstein-Barr Virus (EBV_ mediated cell transformation is a key step in the development of several cancers including Burkitt’s lymphoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma and others. EBNA1 is expressed in all virally infected tumour cells and has a key role in viral genome propagation and transmission. In addition it plays a central role in cell survival and viral oncogenesis. EBNA1 interacts with several protein partners to achieve its functions. In the present study we aimed to explore the details of such protein-protein interactions using both in vitro and in silico methodologies. Due to its unusual sequence, it has not been possible to crystalize the full length EBNA1 protein, which has only been achieved for the C-terminal half. Therefore, in order to construct and in silico model of the complete protein in both monomeric and dimeric forms, different molecular modelling and docking strategies were employed. This was used to predict the residues involved in dimer formation and in binding to partner proteins. The best simulations, selected on the basis of global scoring and other thermodynamical parameters, are in agreement with previous empirical studies delineating the structural and physico-chemical characteristics of the EBNA1 molecule. In a parallel approach, the technique of peptide array is being used to investigate critical binding regions of EBNA1 to the partner proteins, including EBNA1 binding protein 2 (EBP2), USP7 and casein kinase 2 (CK2). Briefly, using the partner proteins on the 25-mer EBNA1 peptides not only confirmed previously known regions of binding but also enabled the identification of minimal binding sites and new binding regions. These data will inform future therapeutic approaches targeting EBNA1 in EBV associated diseases.

• Item Type: Conference or Workshop Item
• Status: Published
• Refereed: No
• Glasgow Author(s) Enlighten ID: Wilson, Professor Joanna and Gatherer, Dr Derek and Baillie, Professor George
• Authors: Hussain, M., Baillie, G., Gatherer, D., and Wilson, J.B.
• Subjects: Q Science > QR Microbiology > QR355 Virology
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Life Sciences; College of Medical Veterinary and Life Sciences > School of Molecular Biosciences