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Functional characterisation of the N-terminal domain of polyomavirus large T antigen

Knoblich, Konstantin (2010)
Ph.D. thesis, University of Birmingham.

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Although scientists have extensively researched the relationship between viral oncoproteins and cellular tumour suppressor proteins in recent years, the molecular interactions between these proteins is still poorly understood. It is the goal of this thesis to establish the key elements of specific interactions, in particular to characterise the interaction between the N-terminal part of the viral murine polyoma oncoprotein large T antigen (PyLTNT), and the cellular human regulator protein retinoblastoma (pRb). The homologous SV40 large T antigen protein has been studied thoroughly in recent decades, and has been associated with mesothelioma, osteosarcoma and brain tumours.However, the murine polyomavirus encodes for 154 additional amino acids that are rich in glycine and proline residues and could potentially play an important role towards cell transformation. Moreover, the polyoma virus protein has not been studied to this extent before, and structural and binding experiments conducted here reveal that it remains functional while natively unfolded. Nuclear Magnetic Resonance (NMR) spectroscopy was employed to characterise the protein's motional properties in its native state. A large part of the backbone residues was assigned, and regions interacting with pRb formed a localised structure. The determination of polyomavirus regions associated with retinoblastoma (PRAR) between residues 131 to 137 and to 181 have never been observed and represents a significant advance.

Type of Work:Ph.D. thesis.
Supervisor(s):Günther, Ulrich and Overduin, Michael
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Cancer Studies
Subjects:RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Institution:University of Birmingham
ID Code:600
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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