Natively unfolded human prothymosin alpha adopts partially folded collapsed conformation at acidic pH

Prothymosin alpha has previously been shown to be unfolded at neutral pH, t hus belonging to a growing family of "natively unfolded" proteins. The stru ctural properties and conformational stability of recombinant human prothym osin alpha were characterized:ar neutral and acidic pH by gel filtration, S AXS, circular dichroism, ANS fluorescence, H-1 NMR, and resistance: to urea -induced unfolding. Interestingly, prothymosin alpha underwent a cooperativ e transition from: the unfolded state into a partially folded conformation on lowering the pH. This conformation of prothymosin alpha is a compact den atured state, with structural properties different from those of the molten globule. The formation of alpha-helical structure by the glutamic acid-ric h elements of the protein accompanied by the partial hydrophobic collapse i s expected at lower pH due to the neutralization of the negatively charged residues. It is possible that such conformational changes may be associated with the protein function.