Atomic structure and hierarchical assembly of a cross-β amyloid fibril
10.1073/pnas.1219476110
Crossref journal-article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences (341)
Abstract

The cross-β amyloid form of peptides and proteins represents an archetypal and widely accessible structure consisting of ordered arrays of β-sheet filaments. These complex aggregates have remarkable chemical and physical properties, and the conversion of normally soluble functional forms of proteins into amyloid structures is linked to many debilitating human diseases, including several common forms of age-related dementia. Despite their importance, however, cross-β amyloid fibrils have proved to be recalcitrant to detailed structural analysis. By combining structural constraints from a series of experimental techniques spanning five orders of magnitude in length scale—including magic angle spinning nuclear magnetic resonance spectroscopy, X-ray fiber diffraction, cryoelectron microscopy, scanning transmission electron microscopy, and atomic force microscopy—we report the atomic-resolution (0.5 Å) structures of three amyloid polymorphs formed by an 11-residue peptide. These structures reveal the details of the packing interactions by which the constituent β-strands are assembled hierarchically into protofilaments, filaments, and mature fibrils.

Bibliography

Fitzpatrick, A. W. P., Debelouchina, G. T., Bayro, M. J., Clare, D. K., Caporini, M. A., Bajaj, V. S., Jaroniec, C. P., Wang, L., Ladizhansky, V., Müller, S. A., MacPhee, C. E., Waudby, C. A., Mott, H. R., De Simone, A., Knowles, T. P. J., Saibil, H. R., Vendruscolo, M., Orlova, E. V., Griffin, R. G., & Dobson, C. M. (2013). Atomic structure and hierarchical assembly of a cross-β amyloid fibril. Proceedings of the National Academy of Sciences, 110(14), 5468–5473.

Authors 20
  1. Anthony W. P. Fitzpatrick (first)
  2. Galia T. Debelouchina (additional)
  3. Marvin J. Bayro (additional)
  4. Daniel K. Clare (additional)
  5. Marc A. Caporini (additional)
  6. Vikram S. Bajaj (additional)
  7. Christopher P. Jaroniec (additional)
  8. Luchun Wang (additional)
  9. Vladimir Ladizhansky (additional)
  10. Shirley A. Müller (additional)
  11. Cait E. MacPhee (additional)
  12. Christopher A. Waudby (additional)
  13. Helen R. Mott (additional)
  14. Alfonso De Simone (additional)
  15. Tuomas P. J. Knowles (additional)
  16. Helen R. Saibil (additional)
  17. Michele Vendruscolo (additional)
  18. Elena V. Orlova (additional)
  19. Robert G. Griffin (additional)
  20. Christopher M. Dobson (additional)
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Dates
Type When
Created 12 years, 5 months ago (March 20, 2013, 12:02 a.m.)
Deposited 3 years, 2 months ago (June 7, 2022, 6:15 a.m.)
Indexed 2 hours, 10 minutes ago (Aug. 30, 2025, 1:19 p.m.)
Issued 12 years, 5 months ago (March 19, 2013)
Published 12 years, 5 months ago (March 19, 2013)
Published Online 12 years, 5 months ago (March 19, 2013)
Published Print 12 years, 4 months ago (April 2, 2013)
Funders 0

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@article{Fitzpatrick_2013, title={Atomic structure and hierarchical assembly of a cross-β amyloid fibril}, volume={110}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1219476110}, DOI={10.1073/pnas.1219476110}, number={14}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Fitzpatrick, Anthony W. P. and Debelouchina, Galia T. and Bayro, Marvin J. and Clare, Daniel K. and Caporini, Marc A. and Bajaj, Vikram S. and Jaroniec, Christopher P. and Wang, Luchun and Ladizhansky, Vladimir and Müller, Shirley A. and MacPhee, Cait E. and Waudby, Christopher A. and Mott, Helen R. and De Simone, Alfonso and Knowles, Tuomas P. J. and Saibil, Helen R. and Vendruscolo, Michele and Orlova, Elena V. and Griffin, Robert G. and Dobson, Christopher M.}, year={2013}, month=mar, pages={5468–5473} }