Molecular basis for amyloid-[beta] polymorphism
Abstract
Amyloid-beta (A{beta}) aggregates are the main constituent of senile plaques, the histological hallmark of Alzheimer's disease. A{beta} molecules form {beta}-sheet containing structures that assemble into a variety of polymorphic oligomers, protofibers, and fibers that exhibit a range of lifetimes and cellular toxicities. This polymorphic nature of A{beta} has frustrated its biophysical characterization, its structural determination, and our understanding of its pathological mechanism. To elucidate A{beta} polymorphism in atomic detail, we determined eight new microcrystal structures of fiber-forming segments of A{beta}. These structures, all of short, self-complementing pairs of {beta}-sheets termed steric zippers, reveal a variety of modes of self-association of A{beta}. Combining these atomic structures with previous NMR studies allows us to propose several fiber models, offering molecular models for some of the repertoire of polydisperse structures accessible to A{beta}. These structures and molecular models contribute fundamental information for understanding A{beta} polymorphic nature and pathogenesis.
- Authors:
-
- UCLA
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- NIHHHMI
- OSTI Identifier:
- 1027667
- Resource Type:
- Journal Article
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 108; Journal Issue: 41; Journal ID: ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; FIBERS; MOLECULAR MODELS; PATHOGENESIS
Citation Formats
Colletier, Jacques-Philippe, Laganowsky, Arthur, Landau, Meytal, Zhao, Minglei, Soriaga, Angela B, Goldschmidt, Lukasz, Flot, David, Cascio, Duilio, Sawaya, Michael R, Eisenberga, David, and ESRF). Molecular basis for amyloid-[beta] polymorphism. United States: N. p., 2011.
Web. doi:10.1073/pnas.1112600108.
Colletier, Jacques-Philippe, Laganowsky, Arthur, Landau, Meytal, Zhao, Minglei, Soriaga, Angela B, Goldschmidt, Lukasz, Flot, David, Cascio, Duilio, Sawaya, Michael R, Eisenberga, David, & ESRF). Molecular basis for amyloid-[beta] polymorphism. United States. https://doi.org/10.1073/pnas.1112600108
Colletier, Jacques-Philippe, Laganowsky, Arthur, Landau, Meytal, Zhao, Minglei, Soriaga, Angela B, Goldschmidt, Lukasz, Flot, David, Cascio, Duilio, Sawaya, Michael R, Eisenberga, David, and ESRF). 2011.
"Molecular basis for amyloid-[beta] polymorphism". United States. https://doi.org/10.1073/pnas.1112600108.
@article{osti_1027667,
title = {Molecular basis for amyloid-[beta] polymorphism},
author = {Colletier, Jacques-Philippe and Laganowsky, Arthur and Landau, Meytal and Zhao, Minglei and Soriaga, Angela B and Goldschmidt, Lukasz and Flot, David and Cascio, Duilio and Sawaya, Michael R and Eisenberga, David and ESRF)},
abstractNote = {Amyloid-beta (A{beta}) aggregates are the main constituent of senile plaques, the histological hallmark of Alzheimer's disease. A{beta} molecules form {beta}-sheet containing structures that assemble into a variety of polymorphic oligomers, protofibers, and fibers that exhibit a range of lifetimes and cellular toxicities. This polymorphic nature of A{beta} has frustrated its biophysical characterization, its structural determination, and our understanding of its pathological mechanism. To elucidate A{beta} polymorphism in atomic detail, we determined eight new microcrystal structures of fiber-forming segments of A{beta}. These structures, all of short, self-complementing pairs of {beta}-sheets termed steric zippers, reveal a variety of modes of self-association of A{beta}. Combining these atomic structures with previous NMR studies allows us to propose several fiber models, offering molecular models for some of the repertoire of polydisperse structures accessible to A{beta}. These structures and molecular models contribute fundamental information for understanding A{beta} polymorphic nature and pathogenesis.},
doi = {10.1073/pnas.1112600108},
url = {https://www.osti.gov/biblio/1027667},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
issn = {0027-8424},
number = 41,
volume = 108,
place = {United States},
year = {Wed Oct 19 00:00:00 EDT 2011},
month = {Wed Oct 19 00:00:00 EDT 2011}
}