Trimethylamine-N-oxide-induced folding of alpha-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.
Uversky
V N
VN
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA. uversky@hydrogen.ucsc.edu
Li
J
J
Fink
A L
AL
D000178:Acrylamides / Q000494:pharmacology; D002942:Circular Dichroism; D004305:Dose-Response Relationship, Drug; D008744:Methylamines / Q000737:chemistry* / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D016877:Oxidants / Q000737:chemistry* / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000378:metabolism; D012542:Scattering, Radiation; D013050:Spectrometry, Fluorescence; D051843:Synucleins; D013997:Time Factors; D014965:X-Rays; D051844:alpha-Synuclein
D000178:Acrylamides; D008744:Methylamines; D009419:Nerve Tissue Proteins; D016877:Oxidants; D010455:Peptides; D011994:Recombinant Proteins; D051843:Synucleins; D051844:alpha-Synuclein; C005855:trimethyloxamine