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標題: Amyloid-like fibril formation in an all beta-barrel protein - Partially structured intermediate state(s) is a precursor for fibril formation
作者: Srisailam, S.
Krishnaswamy, T.
Kumar, T.K.S.
Rajalingam, D.
Kathir, K.M.
Sheu, H.S.
Jan, F.J.
Chao, P.C.
Yu, C.
關鍵字: fibroblast-growth-factor;alpha-synuclein;electron-microscopy;parkinsons-disease;globular-protein;human lysozyme;in-vitro;aggregation;prion;insulin
Project: Journal of Biological Chemistry
期刊/報告no:: Journal of Biological Chemistry, Volume 278, Issue 20, Page(s) 17701-17709.
Acidic fibroblast growth factor from newt (Notopthalmus viridescens) is a similar to15-kDa, all beta-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-beta structure with an average diameter of 10-15 Angstrom. 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 beta-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 beta-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 "sticky" 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 beta-sheet formation among the extended, linear beta-strands in the protein.
ISSN: 0021-9258
DOI: 10.1074/jbc.M300336200
Appears in Collections:植物病理學系

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