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    Structures of Oligomers of a Peptide from β-Amyloid
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    † Department of Chemistry, University of California, Irvine, Irvine, California 92697-2025, United States
    ‡ Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, California 92697-3900, United States
    § Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, California 92697-3900, United States
    [email protected]
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    Journal of the American Chemical Society

    Cite this: J. Am. Chem. Soc. 2013, 135, 33, 12460–12467
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    https://doi.org/10.1021/ja4068854
    Published August 8, 2013
    Copyright © 2013 American Chemical Society
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    Abstract

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    Amyloid oligomers play a central role in Alzheimer’s and other amyloid diseases, and yet the structures of these heterogeneous and unstable species are not well understood. To better understand the structures of oligomers formed by amyloid-β peptide (Aβ), we have incorporated a key amyloidogenic region of Aβ into a macrocyclic peptide that stabilizes oligomers and facilitates structural elucidation by X-ray crystallography. This paper reports the crystallographic structures of oligomers and oligomer assemblies formed by a macrocycle containing the Aβ15–23 nonapeptide. The macrocycle forms hydrogen-bonded β-sheets that assemble into cruciform tetramers consisting of eight β-strands in a two-layered assembly. Three of the cruciform tetramers assemble into a triangular dodecamer. These oligomers further assemble in the lattice to form hexagonal pores. Molecular modeling studies suggest that the natural Aβ peptide can form similar oligomers and oligomer assemblies. The crystallographic and molecular modeling studies suggest the potential for interaction of the oligomers with cell membranes and provide insights into the role of oligomers in amyloid diseases.

    Copyright © 2013 American Chemical Society

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    Crystallographic data in CIF format and details of the synthesis and crystallization of macrocyclic β-sheet peptide 1, X-ray diffraction data collection, processing, and structure and refinement, and modeling of oligomers of linear peptide 2. This material is available free of charge via the Internet at http://pubs.acs.org. The crystal structure of QKLVFFAED nonapeptide segment was deposited into the Protein Data Bank (PDB) with PDB code 4IVH.

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    9. Patrick J. Salveson, Ryan K. Spencer, and James S. Nowick . X-ray Crystallographic Structure of Oligomers Formed by a Toxic β-Hairpin Derived from α-Synuclein: Trimers and Higher-Order Oligomers. Journal of the American Chemical Society 2016, 138 (13) , 4458-4467. https://doi.org/10.1021/jacs.5b13261
    10. Thanh D. Do, Nichole E. LaPointe, Rebecca Nelson, Pascal Krotee, Eric Y. Hayden, Brittany Ulrich, Sarah Quan, Stuart C. Feinstein, David B. Teplow, David Eisenberg, Joan-Emma Shea, and Michael T. Bowers . Amyloid β-Protein C-Terminal Fragments: Formation of Cylindrins and β-Barrels. Journal of the American Chemical Society 2016, 138 (2) , 549-557. https://doi.org/10.1021/jacs.5b09536
    11. Johnny D. Pham, Ryan K. Spencer, Kevin H. Chen, and James S. Nowick . A Fibril-Like Assembly of Oligomers of a Peptide Derived from β-Amyloid. Journal of the American Chemical Society 2014, 136 (36) , 12682-12690. https://doi.org/10.1021/ja505713y
    12. Kristoffer Brännström, Anders Öhman, Lina Nilsson, Mathias Pihl, Linda Sandblad, and Anders Olofsson . The N-terminal Region of Amyloid β Controls the Aggregation Rate and Fibril Stability at Low pH Through a Gain of Function Mechanism. Journal of the American Chemical Society 2014, 136 (31) , 10956-10964. https://doi.org/10.1021/ja503535m
    13. Ryan K. Spencer, Hao Li, and James S. Nowick . X-ray Crystallographic Structures of Trimers and Higher-Order Oligomeric Assemblies of a Peptide Derived from Aβ17–36. Journal of the American Chemical Society 2014, 136 (15) , 5595-5598. https://doi.org/10.1021/ja5017409
    14. Johnny D. Pham, Borries Demeler, and James S. Nowick . Polymorphism of Oligomers of a Peptide from β-Amyloid. Journal of the American Chemical Society 2014, 136 (14) , 5432-5442. https://doi.org/10.1021/ja500996d
    15. Nathan A Bernhardt, Workalemahu M. Berhanu, and Ulrich H. E. Hansmann . Mutations and Seeding of Amylin Fibril-Like Oligomers. The Journal of Physical Chemistry B 2013, 117 (50) , 16076-16085. https://doi.org/10.1021/jp409777p
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    40. Jonathan E. Ross, Peter C. Knipe, Sam Thompson, Andrew D. Hamilton. Hybrid Diphenylalkyne–Dipeptide Oligomers Induce Multistrand β‐Sheet Formation. Chemistry – A European Journal 2015, 21 (39) , 13518-13521. https://doi.org/10.1002/chem.201502690
    41. Ryan K. Spencer, James S. Nowick. A Newcomer′s Guide to Peptide Crystallography. Israel Journal of Chemistry 2015, 55 (6-7) , 698-710. https://doi.org/10.1002/ijch.201400179
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    43. Bidyut Sarkar, Venus Singh Mithu, Bappaditya Chandra, Arghya Mandal, Muralidharan Chandrakesan, Debanjan Bhowmik, Perunthiruthy K. Madhu, Sudipta Maiti. Significant Structural Differences between Transient Amyloid‐β Oligomers and Less‐Toxic Fibrils in Regions Known To Harbor Familial Alzheimer′s Mutations. Angewandte Chemie International Edition 2014, 53 (27) , 6888-6892. https://doi.org/10.1002/anie.201402636
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    46. Subramaniam Boopathi, Ponmalai Kolandaivel. Role of zinc and copper metal ions in amyloid β-peptides Aβ 1–40 and Aβ 1–42 aggregation. RSC Adv. 2014, 4 (73) , 38951-38965. https://doi.org/10.1039/C4RA05390G
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    Cite this: J. Am. Chem. Soc. 2013, 135, 33, 12460–12467
    Click to copy citationCitation copied!
    https://doi.org/10.1021/ja4068854
    Published August 8, 2013
    Copyright © 2013 American Chemical Society
    Request reuse permissions

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