PMID:19264960

Citation	Zhang, R, Hu, X, Khant, H, Ludtke, SJ, Chiu, W, Schmid, MF, Frieden, C and Lee, JM (2009) Interprotofilament interactions between Alzheimer's Abeta1-42 peptides in amyloid fibrils revealed by cryoEM. Proc. Natl. Acad. Sci. U.S.A. 106:4653-8
Abstract	Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of amyloid plaques in the brain. This amyloid primarily contains amyloid-beta (Abeta), a 39- to 43-aa peptide derived from the proteolytic cleavage of the endogenous amyloid precursor protein. The 42-residue-length Abeta peptide (Abeta(1-42)), the most abundant Abeta peptide found in plaques, has a much greater propensity to self-aggregate into fibrils than the other peptides and is believed to be more pathogenic. Synthetic human Abeta(1-42) peptides self-aggregate into stable but poorly-ordered helical filaments. We determined their structure to approximately 10-A resolution by using cryoEM and the iterative real-space reconstruction method. This structure reveals 2 protofilaments winding around a hollow core. Previous hairpin-like NMR models for Abeta(17-42) fit well in the cryoEM density map and reveal that the juxtaposed protofilaments are joined via the N terminus of the peptide from 1 protofilament connecting to the loop region of the peptide in the opposite protofilament. This model of mature Abeta(1-42) fibrils is markedly different from previous cryoEM models of Abeta(1-40) fibrils. In our model, the C terminus of Abeta forms the inside wall of the hollow core, which is supported by partial proteolysis analysis.
Links	PubMed PMC2660777 Online version:10.1073/pnas.0901085106
Keywords	Amino Acid Sequence; Amyloid/metabolism; Amyloid/ultrastructure; Amyloid beta-Peptides/chemistry; Amyloid beta-Peptides/metabolism; Amyloid beta-Peptides/ultrastructure; Cryoelectron Microscopy; Humans; Models, Molecular; Molecular Sequence Data; Peptide Fragments/chemistry; Peptide Fragments/metabolism; Peptide Fragments/ultrastructure; Peptides/metabolism; Protein Processing, Post-Translational; Static Electricity
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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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