Amyloid fibrils from the mammalian protein prothymosin alpha.
Mammalian prothymosin alpha, a small (12 kDa) and extremely acidic protein (pI 3.5), is a member of the growing family of 'natively' unfolded proteins. We demonstrate that at low pH ( approximately 3) and high concentrations, prothymosin alpha is capable of forming regular elongated fibrils with flat ribbon structure 4-5 nm in height and 12-13 nm in width as judged from scanning force and electron microscopy. These aggregates induced a characteristic spectral shift of thioflavin T fluorescence and their circular dichroism spectra were indicative of significant beta-sheet content, suggesting formation of classical amyloid. Our findings indicate that natively unfolded proteins may have a general propensity to form amyloid fibrils under conditions inducing partially folded conformations.
Pavlov
Nikolai A
NA
Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Cherny
Dmitry I
DI
Heim
Gudrun
G
Jovin
Thomas M
TM
Subramaniam
Vinod
V
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D052160:Benzothiazoles; D002942:Circular Dichroism; D005456:Fluorescent Dyes / Q000032:analysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D018625:Microscopy, Atomic Force; D008854:Microscopy, Electron; D017510:Protein Folding; D011498:Protein Precursors / Q000737:chemistry* / Q000302:isolation & purification; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D013844:Thiazoles / Q000032:analysis*; D013947:Thymosin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000302:isolation & purification
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D011498:Protein Precursors; D013844:Thiazoles; C040782:prothymosin alpha; C009462:thioflavin T; D013947:Thymosin