Abstract
A study of the effect of trimethylamine Nโoxide on the stability of two recombinant forms of the prion protein PrP, an ovine fullโlength and a human truncated form, is here reported. Both thermal denaturation and denaturation at room temperature were analyzed at pH values above and below the pKa of trimethylamine Nโoxide, which is close to 4.7. Surprisingly, results showed that not only is trimethylamine Nโoxide able to decrease PrP thermal stability at low pH but it also acts as a strong denaturant at room temperature. Likely, this destabilization is due to the capability of the cationic form of trimethylamine Nโoxide to interact with the protein backbone as well as to weaken electrostatic interactions which are important for PrP fold. These results constitute the first experimental measurement of the effect of trimethylamine Nโoxide on PrP stability and provide an unambiguous proof of the destabilizing effect of this osmolyte on PrP at low pH. ยฉ 2006 Wiley Periodicals, Inc. Biopolymers 82: 234โ240, 2006
This article was originally published online as an accepted preprint. The โPublished Onlineโ date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at [email protected]