PMID:21949245

Citation	Colletier, JP, Laganowsky, A, Landau, M, Zhao, M, Soriaga, AB, Goldschmidt, L, Flot, D, Cascio, D, Sawaya, MR and Eisenberg, D (2011) Molecular basis for amyloid-beta polymorphism. Proc. Natl. Acad. Sci. U.S.A. 108:16938-43
Abstract	Amyloid-beta (Aβ) aggregates are the main constituent of senile plaques, the histological hallmark of Alzheimer's disease. Aβ molecules form β-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 Aβ has frustrated its biophysical characterization, its structural determination, and our understanding of its pathological mechanism. To elucidate Aβ polymorphism in atomic detail, we determined eight new microcrystal structures of fiber-forming segments of Aβ. These structures, all of short, self-complementing pairs of β-sheets termed steric zippers, reveal a variety of modes of self-association of Aβ. 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 Aβ. These structures and molecular models contribute fundamental information for understanding Aβ polymorphic nature and pathogenesis.
Links	PubMed PMC3193189 Online version:10.1073/pnas.1112600108
Keywords	Alzheimer Disease/etiology; Alzheimer Disease/metabolism; Amino Acid Sequence; Amyloid beta-Peptides/chemistry; Amyloid beta-Peptides/genetics; Amyloid beta-Peptides/ultrastructure; Crystallization; Crystallography, X-Ray; Humans; Microscopy, Electron, Transmission; Models, Molecular; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular; Peptide Fragments/chemistry; Peptide Fragments/genetics; Peptide Fragments/ultrastructure; Protein Multimerization; Protein Structure, Secondary
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:A4	enables	GO:0042802: identical protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P05067:PRO_0000000092	F		Seeded From UniProt	complete

References

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