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Distinguishing amyloid fibril structures in Alzheimer's disease (AD) by two-dimensional ultraviolet (2DUV) spectroscopy.

ABSTRACT: Understanding the aggregation mechanism of amyloid fibrils and characterizing their structures are important steps in the investigation of several neurodegenerative disorders associated with the misfolding of proteins. We report a simulation study of coherent two-dimensional chiral signals of three NMR structures of A? protein fibrils associated with Alzheimer's Disease, two models for A?(8-40) peptide wild-type (WT) and one for the Iowa (D23N) A?(15-40) mutant. Both far-ultraviolet (FUV) signals (? = 190-250 nm), which originate from the backbone n?* and ??* transitions, and near-ultraviolet (NUV) signals (? ? 250 nm) associated with aromatic side chains (Phe and Tyr) show distinct cross-peak patterns that can serve as novel signatures for the secondary structure.

SUBMITTER: Lam AR

PROVIDER: S-EPMC3458647 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Distinguishing amyloid fibril structures in Alzheimer's disease (AD) by two-dimensional ultraviolet (2DUV) spectroscopy.

Lam A R AR Jiang J J Mukamel S S

Biochemistry 20111020 45

Understanding the aggregation mechanism of amyloid fibrils and characterizing their structures are important steps in the investigation of several neurodegenerative disorders associated with the misfolding of proteins. We report a simulation study of coherent two-dimensional chiral signals of three NMR structures of Aβ protein fibrils associated with Alzheimer's Disease, two models for Aβ(8-40) peptide wild-type (WT) and one for the Iowa (D23N) Aβ(15-40) mutant. Both far-ultraviolet (FUV) signal ...[more]

PMID: 21961527

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