Expanding the Repertoire of Amyloid Polymorphs by Co-polymerization of Related Protein Precursors
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Griffin_Expanding the repertoire.pdf
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Author(s)
Sarell, Claire J.
Woods, Lucy A.
Su, Yongchao
Debelouchina, Galia Tzvetanova
Ashcroft, Alison E
Griffin, Robert Guy
Stockley, Peter G.
Radford, Sheena E.
Date Issued
January 2013
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry and Molecular Biology (ASBMB)
Citation
Sarell, C. J., L. A. Woods, Y. Su, G. T. Debelouchina, A. E. Ashcroft, R. G. Griffin, P. G. Stockley, and S. E. Radford. “Expanding the Repertoire of Amyloid Polymorphs by Co-polymerization of Related Protein Precursors.” Journal of Biological Chemistry 288, no. 10 (March 8, 2013): 7327-7337. .
Version
Final published version
Abstract
Amyloid fibrils can be generated from proteins with diverse sequences and folds. Although amyloid fibrils assembled in vitro commonly involve a single protein precursor, fibrils formed in vivo can contain more than one protein sequence. How fibril structure and stability differ in fibrils composed of single proteins (homopolymeric fibrils) from those generated by co-polymerization of more than one protein sequence (heteropolymeric fibrils) is poorly understood. Here we compare the structure and stability of homo and heteropolymeric fibrils formed from human β2-microglobulin and its truncated variant ΔN6. We use an array of approaches (limited proteolysis, magic angle spinning NMR, Fourier transform infrared spectroscopy, and fluorescence) combined with measurements of thermodynamic stability to characterize the different fibril types. The results reveal fibrils with different structural properties, different side-chain packing, and strikingly different stabilities. These findings demonstrate how co-polymerization of related precursor sequences can expand the repertoire of structural and thermodynamic polymorphism in amyloid fibrils to an extent that is greater than that obtained by polymerization of a single precursor alone.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Francis Bitter Magnet Laboratory (Massachusetts Institute of Technology)
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DOI of Published Version
https://doi.org/10.1074/jbc.M112.447524
