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Molecular interactions between monoclonal oligomer-specific antibody 5E3 and its amyloid beta cognates

Author

Listed:
  • Massih Khorvash
  • Nick Blinov
  • Carol Ladner-Keay
  • Jie Lu
  • Judith M Silverman
  • Ebrima Gibbs
  • Yu Tian Wang
  • Andriy Kovalenko
  • David Wishart
  • Neil R Cashman

Abstract

Oligomeric amyloid β (Aβ) is currently considered the most neurotoxic form of the Aβ peptide implicated in Alzheimer’s disease (AD). The molecular structures of the oligomers have remained mostly unknown due to their transient nature. As a result, the molecular mechanisms of interactions between conformation-specific antibodies and their Aβ oligomer (AβO) cognates are not well understood. A monoclonal conformation-specific antibody, m5E3, was raised against a structural epitope of Aβ oligomers. m5E3 binds to AβOs with high affinity, but not to Aβ monomers or fibrils. In this study, a computational model of the variable fragment (Fv) of the m5E3 antibody (Fv5E3) is introduced. We further employ docking and molecular dynamics simulations to determine the molecular details of the antibody-oligomer interactions, and to classify the AβOs as Fv5E3-positives and negatives, and to provide a rationale for the low affinity of Fv5E3 for fibrils. This information will help us to perform site-directed mutagenesis on the m5E3 antibody to improve its specificity and affinity toward oligomeric Aβ species. We also provide evidence for the possible capability of the m5E3 antibody to disaggregate AβOs and to fragment protofilaments.

Suggested Citation

  • Massih Khorvash & Nick Blinov & Carol Ladner-Keay & Jie Lu & Judith M Silverman & Ebrima Gibbs & Yu Tian Wang & Andriy Kovalenko & David Wishart & Neil R Cashman, 2020. "Molecular interactions between monoclonal oligomer-specific antibody 5E3 and its amyloid beta cognates," PLOS ONE, Public Library of Science, vol. 15(5), pages 1-35, May.
    • Handle: RePEc:plo:pone00:0232266
    DOI: 10.1371/journal.pone.0232266
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    References listed on IDEAS

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    1. Aroop Sircar & Jeffrey J Gray, 2010. "SnugDock: Paratope Structural Optimization during Antibody-Antigen Docking Compensates for Errors in Antibody Homology Models," PLOS Computational Biology, Public Library of Science, vol. 6(1), pages 1-13, January.
    2. Rebecca Nelson & Michael R. Sawaya & Melinda Balbirnie & Anders Ø. Madsen & Christian Riekel & Robert Grothe & David Eisenberg, 2005. "Structure of the cross-β spine of amyloid-like fibrils," Nature, Nature, vol. 435(7043), pages 773-778, June.
    3. Sylvain Lesné & Ming Teng Koh & Linda Kotilinek & Rakez Kayed & Charles G. Glabe & Austin Yang & Michela Gallagher & Karen H. Ashe, 2006. "RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory," Nature, Nature, vol. 440(7082), pages 352-357, March.
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