Prostate apoptosis response-4 (Par-4) is a pro-apoptotic tumor suppressor protein with significant intrinsic disorder character. Par-4 is unique in the sense that it can selectively induce apoptosis in cancer cells. Down-regulation of this protein has been reported in a myriad of cancers whereas up-regulation is associated with several neurodegenerative disorders. Caspase-dependent intracellular cleavage of Par-4 is essential to produce the functionally active fragment, cl-Par-4 (caspase-cleaved Par-4) which enters the nucleus and inhibits NF-kB-mediated cell survival pathways. Detailed structural information of cl-Par-4 will be helpful in designing a promising strategy to re-establish normal Par-4 activity inside cells. Here, we have employed circular dichroism (CD) spectroscopy and dynamic light scattering (DLS) to analyze the conditions under which cl-Par-4 will be suitable for structural analysis via NMR spectroscopy and X-ray crystallography. We have compared size, secondary structure and solubility of cl-Par-4 as a function of ionic and pH environment. We have also assessed the secondary structure of the D313K point mutant of cl-Par-4. These findings will be helpful in understanding function and for solving the structure of cl-Par-4.

Probing the structure of the caspase-cleaved prostate apoptosis response-4 (cl-Par-4) tumor suppressor

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