Accelerated fibrillation of alpha-synuclein induced by the combined action of macromolecular crowding and factors inducing partial folding.
To better model the characteristics of crowded intracellular environments, we examined the effect of several factors known to induce partial folding and accelerated fibrillation of alpha-synuclein in dilute solutions, on the fibrillation of this protein in a crowded milieu. We found that low pH, certain metals and pesticides, polyanions, polycations and low concentrations of organic solvents cause a significant acceleration of alpha-synuclein fibrillation in the presence of high concentrations of polyethylene glycol. This suggests that the fibril-promoting effects of factors inducing partial folding of alpha-synuclein and the fibril-stimulating effects of macromolecular crowding are relatively independent and thus might act additively or even synergistically.
Munishkina
L A
LA
Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
Fink
A L
AL
Uversky
V N
VN
D000818:Animals; D000838:Anions / Q000494:pharmacology; D055598:Chemical Phenomena; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004926:Escherichia coli; D006025:Glycosaminoglycans / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D046911:Macromolecular Substances / Q000378:metabolism*; D008670:Metals / Q000494:pharmacology; D008744:Methylamines / Q000494:pharmacology; D008854:Microscopy, Electron; D008958:Models, Molecular; D016877:Oxidants / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D055672:Static Electricity; D013997:Time Factors; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure
D000838:Anions; D006025:Glycosaminoglycans; D046911:Macromolecular Substances; D008670:Metals; D008744:Methylamines; D016877:Oxidants; D051844:alpha-Synuclein; D011092:Polyethylene Glycols; C005855:trimethyloxamine