PhD Theses (Biosciences and Bioengineering)

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Probing the structure and dynamics of intrinsically disordered c-Myc PEST fragment using spectroscopic techniques
(2018) Ansari, Mohd. Ziauddin
Intrinsically Disordered Proteins (IDPs) do not have any well-defined stable secondary or tertiary structure under the physiological conditions. Regardless of lacking stable structure, IDPs have several structural and functional advantages over the ordered proteins and participates in many key biological functions such as signaling and cell cycle control. An extensive analysis of the structure, function and dynamics of IDPs is necessary for deciphering the elaborate physiological control of their functions and how such controls might fail in human diseases. In this context, we have chosen an IDP, human c-Myc PEST region whose structural determination and characterization of disordered properties has not been done before. The c-Myc oncoprotein is a highly unstable transcription factor which is involved in many essential cell processes. Its centrally located, PEST region is responsible for quick degradation of c-Myc protein. The exact mechanism of PEST recognition and targeting of PEST containing proteins for degradation via proteasome is poorly understood and structural analysis of PEST region can provide better insights to understand their functional mechanism.