pH-induced folding of an apoptotic coiled coil

Par-4 is a 38-kD protein pivotal to the apoptotic pathways of various cell types, most notably prostate cells and neurons, where it has been linked to prostate cancer and various neurodegenerative disorders including Alzheime r's and Huntington's diseases and HIV encephalitis. The C-terminal region o f Par-4 is responsible for homodimerization and the ability of Par-4 to int eract with proposed effector molecules. In this study, we show that the C-t erminal 47 residues of Par-4 are natively unfolded at physiological pH and temperature. Evidence is rapidly accumulating that natively unfolded protei ns play an important role in various cellular functions and signaling pathw ays, and that folding can often be induced on complexation with effector mo lecules or alteration of environment. Here we use primarily CD studies to s how that changes in the environment, particularly pH and temperature, can i nduce the Par-4 C terminus to form a self-associated coiled coil.