Expanding the Repertoire of Amyloid Polymorphs by Co-polymerization of Related Protein Precursors
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 o...
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| Format: | Article |
| Language: | en_US |
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American Society for Biochemistry and Molecular Biology (ASBMB)
2013
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| Online Access: | http://hdl.handle.net/1721.1/82643 https://orcid.org/0000-0003-1589-832X |
| _version_ | 1826216991722045440 |
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| author | Sarell, Claire J. Woods, Lucy A. Su, Yongchao Debelouchina, Galia Tzvetanova Ashcroft, Alison E Griffin, Robert Guy Stockley, Peter G. Radford, Sheena E. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Sarell, Claire J. Woods, Lucy A. Su, Yongchao Debelouchina, Galia Tzvetanova Ashcroft, Alison E Griffin, Robert Guy Stockley, Peter G. Radford, Sheena E. |
| author_sort | Sarell, Claire J. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T16:56:40Z |
| format | Article |
| id | mit-1721.1/82643 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:56:40Z |
| publishDate | 2013 |
| publisher | American Society for Biochemistry and Molecular Biology (ASBMB) |
| record_format | dspace |
| spelling | mit-1721.1/826432022-10-03T09:16:34Z Expanding the Repertoire of Amyloid Polymorphs by Co-polymerization of Related Protein Precursors Sarell, Claire J. Woods, Lucy A. Su, Yongchao Debelouchina, Galia Tzvetanova Ashcroft, Alison E Griffin, Robert Guy Stockley, Peter G. Radford, Sheena E. Massachusetts Institute of Technology. Department of Chemistry Francis Bitter Magnet Laboratory (Massachusetts Institute of Technology) Griffin, Robert Guy Su, Yongchao 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. National Institutes of Health (U.S.) (Grant EB003151) National Institutes of Health (U.S.) (Grant EB002026) Medical Research Council (Great Britain) (Grant G0900958) Wellcome Trust (London, England) (grant code 075099/Z/04/Z (LCT Premier, mass spectrometry facility) and NMR (094232)) Biotechnology and Biological Sciences Research Council (Great Britain) (BB/E012558/I, for the Synapt HDMS) Biotechnology and Biological Sciences Research Council (Great Britain) (BB/526502/1) 2013-12-05T21:14:42Z 2013-12-05T21:14:42Z 2013-01 Article http://purl.org/eprint/type/JournalArticle 0021-9258 1083-351X http://hdl.handle.net/1721.1/82643 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. . https://orcid.org/0000-0003-1589-832X en_US http://dx.doi.org/10.1074/jbc.M112.447524 Journal of Biological Chemistry Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Society for Biochemistry and Molecular Biology (ASBMB) American Society for Biochemistry and Molecular Biology |
| spellingShingle | Sarell, Claire J. Woods, Lucy A. Su, Yongchao Debelouchina, Galia Tzvetanova Ashcroft, Alison E Griffin, Robert Guy Stockley, Peter G. Radford, Sheena E. Expanding the Repertoire of Amyloid Polymorphs by Co-polymerization of Related Protein Precursors |
| title | Expanding the Repertoire of Amyloid Polymorphs by Co-polymerization of Related Protein Precursors |
| title_full | Expanding the Repertoire of Amyloid Polymorphs by Co-polymerization of Related Protein Precursors |
| title_fullStr | Expanding the Repertoire of Amyloid Polymorphs by Co-polymerization of Related Protein Precursors |
| title_full_unstemmed | Expanding the Repertoire of Amyloid Polymorphs by Co-polymerization of Related Protein Precursors |
| title_short | Expanding the Repertoire of Amyloid Polymorphs by Co-polymerization of Related Protein Precursors |
| title_sort | expanding the repertoire of amyloid polymorphs by co polymerization of related protein precursors |
| url | http://hdl.handle.net/1721.1/82643 https://orcid.org/0000-0003-1589-832X |
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