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Assembly of Peptides Derived from ?-Sheet Regions of ?-Amyloid.

ABSTRACT: In Alzheimer's disease, aggregation of the ?-amyloid peptide (A?) results in the formation of oligomers and fibrils that are associated with neurodegeneration. Aggregation of A? occurs through interactions between different regions of the peptide. This paper and the accompanying paper constitute a two-part investigation of two key regions of A?: the central region and the C-terminal region. These two regions promote aggregation and adopt ?-sheet structure in the fibrils, and may also do so in the oligomers. In this paper, we study the assembly of macrocyclic ?-sheet peptides that contain residues 17-23 (LVFFAED) from the central region and residues 30-36 (AIIGLMV) from the C-terminal region. These peptides assemble to form tetramers. Each tetramer consists of two hydrogen-bonded dimers that pack through hydrophobic interactions in a sandwich-like fashion. Incorporation of a single 15N isotopic label into each peptide provides a spectroscopic probe with which to elucidate the ?-sheet assembly and interaction: 1H,15N HSQC studies facilitate the identification of the monomers and tetramers; 15N-edited NOESY studies corroborate the pairing of the dimers within the tetramers. In the following paper, J. Am. Chem. Soc. 2016, DOI: 10.1021/jacs.6b06001 , we will extend these studies to elucidate the coassembly of the peptides to form heterotetramers.


PROVIDER: S-EPMC5089065 | BioStudies | 2016-01-01


REPOSITORIES: biostudies

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Coassembly of Peptides Derived from β-Sheet Regions of β-Amyloid.

Truex Nicholas L NL   Nowick James S JS  

Journal of the American Chemical Society 20161014 42

In this paper, we investigate the coassembly of peptides derived from the central and C-terminal regions of the β-amyloid peptide (Aβ). In the preceding paper, J. Am. Chem. Soc. 2016, DOI: 10.1021/jacs.6b06000 , we established that peptides containing residues 17-23 (LVFFAED) from the central region of Aβ and residues 30-36 (AIIGLMV) from the C-terminal region of Aβ assemble to form homotetramers consisting of two hydrogen-bonded dimers. Here, we mix these tetramer-forming peptides and determine  ...[more]

Publication: 1/2

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