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A partially folded structure of amyloid-beta(1-40) in an aqueous environment.

ABSTRACT: Aggregation of the A?(1-40) peptide is linked to the development of extracellular plaques characteristic of Alzheimer's disease. While previous studies commonly show the A?(1-40) is largely unstructured in solution, we show that A?(1-40) can adopt a compact, partially folded structure. In this structure (PDB ID: 2LFM), the central hydrophobic region of the peptide forms a 3(10) helix from H13 to D23 and the N- and C-termini collapse against the helix due to the clustering of hydrophobic residues. Helical intermediates have been predicted to be crucial on-pathway intermediates in amyloid fibrillogenesis, and the structure presented here presents a new target for investigation of early events in A?(1-40) fibrillogenesis.

SUBMITTER: Vivekanandan S

PROVIDER: S-EPMC3148408 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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A partially folded structure of amyloid-beta(1-40) in an aqueous environment.

Vivekanandan Subramanian S Brender Jeffrey R JR Lee Shirley Y SY Ramamoorthy Ayyalusamy A

Biochemical and biophysical research communications 20110625 2

Aggregation of the Aβ(1-40) peptide is linked to the development of extracellular plaques characteristic of Alzheimer's disease. While previous studies commonly show the Aβ(1-40) is largely unstructured in solution, we show that Aβ(1-40) can adopt a compact, partially folded structure. In this structure (PDB ID: 2LFM), the central hydrophobic region of the peptide forms a 3(10) helix from H13 to D23 and the N- and C-termini collapse against the helix due to the clustering of hydrophobic residues ...[more]

PMID: 21726530

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