Download | - View final version: Molecular interactions between monoclonal oligomer-specific antibody 5E3 and its amyloid beta cognates (PDF, 1.9 MiB)
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DOI | Resolve DOI: https://doi.org/10.1371/journal.pone.0232266 |
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Author | Search for: Khorvash, Massih; Search for: Blinov, Nick1; Search for: Ladner-Keay, Carol1; Search for: Lu, Jie; Search for: Silverman, Judith M.; Search for: Gibbs, Ebrima; Search for: Wang, Yu Tian; Search for: Kovalenko, Andriy1ORCID identifier: https://orcid.org/0000-0001-5033-4314; Search for: Wishart, David1; Search for: Cashman, Neil R.ORCID identifier: https://orcid.org/0000-0002-0080-1006 |
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Editor | Search for: Rezaei, Human |
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Affiliation | - National Research Council of Canada. Nanotechnology
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Format | Text, Article |
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Subject | amyloid beta protein; epitope; monoclonal antibody; monoclonal antibody 5E3; monomer; oligomer; unclassified drug |
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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 sitedirected 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. |
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Publication date | 2020-05-29 |
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Publisher | Public Library of Science |
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Licence | |
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Language | English |
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Peer reviewed | Yes |
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Export citation | Export as RIS |
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Report a correction | Report a correction (opens in a new tab) |
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Record identifier | 07743eaf-fd48-458a-ae4d-ee0be40d4d65 |
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Record created | 2020-06-19 |
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Record modified | 2020-06-23 |
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