Abstract
Epstein-Barr virus (EBV) is a gammaherpesvirus associated with several human malignancies, including Burkett’s lymphoma, Hodgkin’s disease and nasopharyngeal carcinoma. The main objective of this research proposal is to understand the structure determinants in the Latent membrane protein 1 (LMP1) responsible for triggering signals responsible for the onset of EBV-mediated malignant diseases. In this context, we have cloned, expressed and purified the cytoplasmic C-terminus domain of LMP1, such as CTAR1 and CTAR2; in high yields. Far UV circular dichroism (CD) experiments indicate that major portion(s) of the CTAR1 and CTAR2 domains are unstructured. Complete resonance (1H, 15N, and 13C) assignments in CTAR2 have been achieved using the information content derived from various triple resonance NMR experiments. Three-dimensional structure of CTAR2 shows that the protein is mostly unstructured with a prominent β-loop between residues 22 to 25. Thermal denaturation experiments reveal that CTAR2 interacts with the tumor necrosis factor (TNF) receptor – associated death domain (TRADD). The results obtained in this study provide useful clues for the design of therapeutic principles inhibiting the EBV- induced malignancy..