Trimethylamine-N-oxide-induced folding of α-synuclein

The effect of the natural osmolyte trimethylamine-N-oxide (TMAO) on the structural properties and fibril formation of the natively unfolded protein human alpha -synuclein was studied using several physico-chemical methods. TMAO induced folding of alpha -synuclein: at moderate concentrations, a partially folded intermediate with enhanced propensity for fibrillation accumulated; at higher concentrations, alpha -synuclein was tightly folded and underwent self-association to form oligomers. The latter conformation was significantly helical and probably represents the physiologically folded form of the protein. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.