Prostate apoptosis response-4 (Par-4) is a pro-apoptotic tumor suppressor protein. This 38 kDa predominantly intrinsically disordered protein is cleaved intracellularly by caspase-3 at Asp-131 to generate the 24 kDa functionally active cleaved Par-4 (cl-Par-4) protein. The cl-Par-4 fragment inhibits NF-κB-mediated cell survival pathways and causes selective apoptosis in tumor cells. Here, we have employed circular dichroism (CD) spectroscopy, dynamic light scattering (DLS) , UV-vis spectroscopy and SDS-PAGE techniques to assess the effects of various concentrations of monovalent and divalent salts upon the conformation of the cl-Par-4 fragment. We have shown that cl-Par-4 can be induced to form highly compact and helical structures in the presence of high levels of the monovalent cations, and that a similar conformational state can be induced by a considerably lower concentration of divalent cations. The identity of the salt anion has far less influence than does the cation. Additionally, we have analyzed the mixture of particle sizes that occur under medium salt concentration and found that the formation large particles under low salt conditions is a reversible process. The possible consequences of changes in conformation and self-association state upon formation of cl-Par-4 from the parent full-length Par-4 will be discussed.

Conformational studies of the caspase-cleaved Par-4 (cl-Par-4) tumor suppressor protein in the presence of various ions

ACS Spring Meeting 2021

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