DOI: 10.1073/pnas.250288897. Aβ amyloid fibrils possess a core structure highly resistant to hydrogen exchange

Aβ amyloid fibrils possess a core structure highly resistant to hydrogen exchange

10.1073/pnas.250288897

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

We describe here experiments designed to characterize the secondary structure of amyloid fibrils of the Alzheimer's amyloid plaque peptide Aβ, using hydrogen-deuterium exchange measurements evaluated by mass spectrometry. The results show that ≈50% of the amide protons of the polypeptide backbone of Aβ(1–40) resist exchange in aqueous, neutral pH buffer even after more than 1,000 h of incubation at room temperature. We attribute this extensive, strong protection to H-bonding by residues in core regions of β-sheet structure within the fibril. The backbone amide hydrogens exchange at variable rates, suggesting different degrees of protection within the fibril. These data suggest that it is unlikely that the entire Aβ sequence is involved in H-bonded secondary structure within the amyloid fibril. Future studies using the methods described here should reveal further details of Aβ fibril structure and assembly. These methods also should be amenable to studies of other amyloid fibrils and protein aggregates.

Bibliography

Kheterpal, I., Zhou, S., Cook, K. D., & Wetzel, R. (2000). AÎ² amyloid fibrils possess a core structure highly resistant to hydrogen exchange. Proceedings of the National Academy of Sciences, 97(25), 13597â13601.

Authors 4

Indu Kheterpal (first)
Shaolian Zhou (additional)
Kelsey D. Cook (additional)
Ronald Wetzel (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:44 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 9:27 a.m.)
Indexed	1 month ago (July 25, 2025, 6:39 a.m.)
Issued	24 years, 9 months ago (Nov. 21, 2000)
Published	24 years, 9 months ago (Nov. 21, 2000)
Published Online	24 years, 9 months ago (Nov. 21, 2000)
Published Print	24 years, 8 months ago (Dec. 5, 2000)

Funders 0

None

BibTeX

@article{Kheterpal_2000, title={Aβ amyloid fibrils possess a core structure highly resistant to hydrogen exchange}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.250288897}, DOI={10.1073/pnas.250288897}, number={25}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Kheterpal, Indu and Zhou, Shaolian and Cook, Kelsey D. and Wetzel, Ronald}, year={2000}, month=nov, pages={13597–13601} }

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