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Amyloid-like Fibril Formation in an All β-Barrel Protein
Acidic fibroblast growth factor from newt ( Notopthalmus viridescens ) is a â¼15-kDa, all β-sheet protein devoid of disulfide bonds. In the present study, we investigate the effects of 2,2,2-trifluoroethanol (TFE) on the structure of newt acidic fibroblast growth factor (nFGF-1). The protein aggre...
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Published in: | The Journal of biological chemistry 2003-05, Vol.278 (20), p.17701 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | Acidic fibroblast growth factor from newt ( Notopthalmus viridescens ) is a â¼15-kDa, all β-sheet protein devoid of disulfide bonds. In the present study, we investigate the effects of 2,2,2-trifluoroethanol
(TFE) on the structure of newt acidic fibroblast growth factor (nFGF-1). The protein aggregates maximally in 10% (v/v) TFE.
Congo red and thioflavin T binding experiments suggest that the aggregates induced by TFE have properties resembling the amyloid
fibrils. Transmission electron microscopy and x-ray fiber diffraction data show that the fibrils (induced by TFE) are straight,
unbranched, and have a cross-β structure with an average diameter of 10â15 Ã
. Preformed fibrils (induced by TFE) of nFGF-1
are observed to seed amyloid-like fibril formation in solutions containing the protein (nFGF-1) in the native β-barrel conformation.
Fluorescence, far-UV CD, anilino-8-napthalene sulfonate binding, multidimensional NMR, and Fourier transformed infrared spectroscopy
data reveal that formation of a partially structured intermediate state(s) precedes the onset of the fibrillation process.
The native β-barrel structure of nFGF-1 appears to be disrupted in the partially structured intermediate state(s). The protein
in the partially structured intermediate state(s) is found to be âstickyâ with a solvent-exposed non-polar surface(s). Amyloid
fibril formation appears to occur due to coalescence of the protein in the partially structured intermediate state(s) through
solvent-exposed non-polar surfaces and intermolecular β-sheet formation among the extended, linear β-strands in the protein. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M300336200 |