Natively Unfolded Human Prothymosin α Adopts Partially Folded Collapsed Conformation at Acidic pH

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Abstract
Prothymosin α has previously been shown to be unfolded at neutral pH, thus belonging to a growing family of “natively unfolded” proteins. The structural properties and conformational stability of recombinant human prothymosin α were characterized at neutral and acidic pH by gel filtration, SAXS, circular dichroism, ANS fluorescence, 1H NMR, and resistance to urea-induced unfolding. Interestingly, prothymosin α underwent a cooperative transition from the unfolded state into a partially folded conformation on lowering the pH. This conformation of prothymosin α is a compact denatured state, with structural properties different from those of the molten globule. The formation of α-helical structure by the glutamic acid-rich elements of the protein accompanied by the partial hydrophobic collapse is 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.