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

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

PLOS ONE, 2020, vol. 15, issue 5, 1-35

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.

Date: 2020
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232266 (text/html)
https://journals.plos.org/plosone/article/file?id= ... 32266&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0232266

DOI: 10.1371/journal.pone.0232266

Access Statistics for this article

More articles in PLOS ONE from Public Library of Science
Bibliographic data for series maintained by plosone ().