Protein aggregation processes: In search of the mechanism.
Amyloid formation typically follows a time course in which there is a long lag period followed by a rapid formation of fibrils. In this review, I show that the standard mechanisms of polymerization need to be expanded to consider that the monomeric proteins/peptides involved in amyloid formation are intrinsically disordered and exist as an ensemble of disordered-collapsed states. The review focuses primarily on events which occur in the long lag period defining these as protein folding issues, coupled with formation of oligomers. Experimental methods to explore folding and oligomerization issues over a wide range of protein concentrations using primarily fluorescence and 19F-NMR methods are discussed.
Frieden
Carl
C
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA. frieden@biochem.wustl.edu
D000682:Amyloid / Q000737:chemistry; D000818:Animals; D006801:Humans; D008027:Light; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D015233:Models, Statistical; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012542:Scattering, Radiation; D013050:Spectrometry, Fluorescence / Q000379:methods; D013997:Time Factors
D000682:Amyloid; D010455:Peptides; D011108:Polymers; D011506:Proteins