IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0232266.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232266
    Download Restriction: no
    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0232266&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pone.0232266?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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. "A specific amyloid-β protein assembly in the brain impairs memory," Nature, Nature, vol. 440(7082), pages 352-357, March.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Victor Banerjee & Rajiv K Kar & Aritreyee Datta & Krupakar Parthasarathi & Subhrangsu Chatterjee & Kali P Das & Anirban Bhunia, 2013. "Use of a Small Peptide Fragment as an Inhibitor of Insulin Fibrillation Process: A Study by High and Low Resolution Spectroscopy," PLOS ONE, Public Library of Science, vol. 8(8), pages 1-15, August.
    2. Thillai V. Sekar & Eslam A. Elghonaimy & Katy L. Swancutt & Sebastian Diegeler & Isaac Gonzalez & Cassandra Hamilton & Peter Q. Leung & Jens Meiler & Cristina E. Martina & Michael Whitney & Todd A. Ag, 2023. "Simultaneous selection of nanobodies for accessible epitopes on immune cells in the tumor microenvironment," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Jordan R Willis & Bryan S Briney & Samuel L DeLuca & James E Crowe Jr & Jens Meiler, 2013. "Human Germline Antibody Gene Segments Encode Polyspecific Antibodies," PLOS Computational Biology, Public Library of Science, vol. 9(4), pages 1-14, April.
    4. Begoña López-Arias & Enrique Turiégano & Ignacio Monedero & Inmaculada Canal & Laura Torroja, 2017. "Presynaptic Aβ40 prevents synapse addition in the adult Drosophila neuromuscular junction," PLOS ONE, Public Library of Science, vol. 12(5), pages 1-22, May.
    5. Kübra Kaygisiz & Lena Rauch-Wirth & Arghya Dutta & Xiaoqing Yu & Yuki Nagata & Tristan Bereau & Jan Münch & Christopher V. Synatschke & Tanja Weil, 2023. "Data-mining unveils structure–property–activity correlation of viral infectivity enhancing self-assembling peptides," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Julia Koehler Leman & Sergey Lyskov & Steven M. Lewis & Jared Adolf-Bryfogle & Rebecca F. Alford & Kyle Barlow & Ziv Ben-Aharon & Daniel Farrell & Jason Fell & William A. Hansen & Ameya Harmalkar & Je, 2021. "Ensuring scientific reproducibility in bio-macromolecular modeling via extensive, automated benchmarks," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    7. Vishruth Mullapudi & Jaime Vaquer-Alicea & Vaibhav Bommareddy & Anthony R. Vega & Bryan D. Ryder & Charles L. White & Marc. I. Diamond & Lukasz A. Joachimiak, 2023. "Network of hotspot interactions cluster tau amyloid folds," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    8. Maher A Dayeh & George Livadiotis & Saber Elaydi, 2018. "A discrete mathematical model for the aggregation of β-Amyloid," PLOS ONE, Public Library of Science, vol. 13(5), pages 1-13, May.
    9. Deena M A Gendoo & Paul M Harrison, 2011. "Origins and Evolution of the HET-s Prion-Forming Protein: Searching for Other Amyloid-Forming Solenoids," PLOS ONE, Public Library of Science, vol. 6(11), pages 1-12, November.
    10. Xiaohang Li & Jin Cui & Yang Yu & Wei Li & Yujun Hou & Xin Wang & Dapeng Qin & Cun Zhao & Xinsheng Yao & Jian Zhao & Gang Pei, 2016. "Traditional Chinese Nootropic Medicine Radix Polygalae and Its Active Constituent Onjisaponin B Reduce β-Amyloid Production and Improve Cognitive Impairments," PLOS ONE, Public Library of Science, vol. 11(3), pages 1-19, March.
    11. Andrew C Gill, 2014. "β-Hairpin-Mediated Formation of Structurally Distinct Multimers of Neurotoxic Prion Peptides," PLOS ONE, Public Library of Science, vol. 9(1), pages 1-17, January.
    12. Jeffrey A. Ruffolo & Lee-Shin Chu & Sai Pooja Mahajan & Jeffrey J. Gray, 2023. "Fast, accurate antibody structure prediction from deep learning on massive set of natural antibodies," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    13. Allen W Bryan Jr. & Matthew Menke & Lenore J Cowen & Susan L Lindquist & Bonnie Berger, 2009. "BETASCAN: Probable β-amyloids Identified by Pairwise Probabilistic Analysis," PLOS Computational Biology, Public Library of Science, vol. 5(3), pages 1-11, March.
    14. Thomas Heerde & Desiree Schütz & Yu-Jie Lin & Jan Münch & Matthias Schmidt & Marcus Fändrich, 2023. "Cryo-EM structure and polymorphic maturation of a viral transduction enhancing amyloid fibril," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    15. Sanne Abeln & Michele Vendruscolo & Christopher M Dobson & Daan Frenkel, 2014. "A Simple Lattice Model That Captures Protein Folding, Aggregation and Amyloid Formation," PLOS ONE, Public Library of Science, vol. 9(1), pages 1-8, January.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0232266. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.