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

التفاصيل البيبلوغرافية
العنوان: Molecular interactions between monoclonal oligomer-specific antibody 5E3 and its amyloid beta cognates.
المؤلفون: Massih Khorvash, Nick Blinov, Carol Ladner-Keay, Jie Lu, Judith M Silverman, Ebrima Gibbs, Yu Tian Wang, Andriy Kovalenko, David Wishart, Neil R Cashman
المصدر: PLoS ONE, Vol 15, Iss 5, p e0232266 (2020)
بيانات النشر: Public Library of Science (PLoS), 2020.
سنة النشر: 2020
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0232266
URL الوصول: https://doaj.org/article/2c215e5099454e898408e8dcb10a70d5
رقم الأكسشن: edsdoj.2c215e5099454e898408e8dcb10a70d5
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0232266