Articles written in Journal of Chemical Sciences

    • Ordered structure induced in human c-Myc PEST region upon forming a disulphide bonded dimer


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      PEST rich protein sequences are intrinsically disordered and serve as degradation hotspots in eukaryotic cells. The structure of PEST degrons in proteins and their mechanism of action remain poorly understood. Deregulation or overexpression of human transcription factor c-Myc causes cancer. The PEST region in c-Myc is implicated for its rapid degradation. Here, we investigate how the structure of 77-residue PEST fragment of c-Myc and its mutant (M1, Trp inserted) are affected by the formation of a covalent dimer. DLS and size exclusion data indicated a ~30% increase in Stokes radius upon the formation of the dimer. CD showed an increase in helix and strand content with dimer formation in both Wt and mutant. However,counterintuitively, Trp fluorescence anisotropy decay was marginally faster in the dimer compared to monomer. This anomaly was traced to Trp-Trp Fo¨rster resonance energy homotransfer in M1 dimer, suggesting close interaction between two chains in the dimer. Our data suggest that indole rings in the PEST M1 dimer are no further than 24 A ° apart. These results may hold the key to higher stability of c-Myc in tumours and the poorly understood physiological role of c-Myc oligomer in cells.

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