Propagating structure of Alzheimer’s β-amyloid (10–35) is parallel β-sheet with residues in exact register
10.1073/pnas.95.23.13407
Crossref journal-article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences (341)
Abstract

The pathognomonic plaques of Alzheimer’s disease are composed primarily of the 39- to 43-aa β-amyloid (Aβ) peptide. Crosslinking of Aβ peptides by tissue transglutaminase (tTg) indicates that Gln 15 of one peptide is proximate to Lys 16 of another in aggregated Aβ. Here we report how the fibril structure is resolved by mapping interstrand distances in this core region of the Aβ peptide chain with solid-state NMR. Isotopic substitution provides the source points for measuring distances in aggregated Aβ. Peptides containing a single carbonyl 13 C label at Gln 15 , Lys 16 , Leu 17 , or Val 18 were synthesized and evaluated by NMR dipolar recoupling methods for the measurement of interpeptide distances to a resolution of 0.2 Å. Analysis of these data establish that this central core of Aβ consists of a parallel β-sheet structure in which identical residues on adjacent chains are aligned directly, i.e., in register. Our data, in conjunction with existing structural data, establish that the Aβ fibril is a hydrogen-bonded, parallel β-sheet defining the long axis of the Aβ fibril propagation.

Bibliography

Benzinger, T. L. S., Gregory, D. M., Burkoth, T. S., Miller-Auer, H., Lynn, D. G., Botto, R. E., & Meredith, S. C. (1998). Propagating structure of Alzheimer’s β-amyloid (10–35) is parallel β-sheet with residues in exact register. Proceedings of the National Academy of Sciences, 95(23), 13407–13412.

Authors 7
  1. Tammie L. S. Benzinger (first)
  2. David M. Gregory (additional)
  3. Timothy S. Burkoth (additional)
  4. Hélène Miller-Auer (additional)
  5. David G. Lynn (additional)
  6. Robert E. Botto (additional)
  7. Stephen C. Meredith (additional)
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Dates
Type When
Created 23 years, 1 month ago (July 26, 2002, 10:40 a.m.)
Deposited 3 years, 4 months ago (April 13, 2022, 5:03 p.m.)
Indexed 1 day, 10 hours ago (Aug. 26, 2025, 2:29 a.m.)
Issued 26 years, 9 months ago (Nov. 10, 1998)
Published 26 years, 9 months ago (Nov. 10, 1998)
Published Online 26 years, 9 months ago (Nov. 10, 1998)
Published Print 26 years, 9 months ago (Nov. 10, 1998)
Funders 0

None

@article{Benzinger_1998, title={Propagating structure of Alzheimer’s β-amyloid (10–35) is parallel β-sheet with residues in exact register}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.23.13407}, DOI={10.1073/pnas.95.23.13407}, number={23}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Benzinger, Tammie L. S. and Gregory, David M. and Burkoth, Timothy S. and Miller-Auer, Hélène and Lynn, David G. and Botto, Robert E. and Meredith, Stephen C.}, year={1998}, month=nov, pages={13407–13412} }