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Capturing transient antibody conformations with DNA origami epitopes

Author

Listed:
  • Ping Zhang

    (University of Chinese Academy of Sciences)

  • Xiaoguo Liu

    (Institute of Translational Medicine)

  • Pi Liu

    (Nankai University
    Chinese Academy of Sciences)

  • Fei Wang

    (Institute of Translational Medicine
    Southern Medical University Affiliated Fengxian Hospital)

  • Hirotaka Ariyama

    (Kanazawa University)

  • Toshio Ando

    (Kanazawa University)

  • Jianping Lin

    (Nankai University
    Chinese Academy of Sciences)

  • Lihua Wang

    (Chinese Academy of Sciences
    East China Normal University)

  • Jun Hu

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Bin Li

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Chunhai Fan

    (Institute of Translational Medicine
    Shanghai Jiao Tong University)

Abstract

Revealing antibody-antigen interactions at the single-molecule level will deepen our understanding of immunology. However, structural determination under crystal or cryogenic conditions does not provide temporal resolution for resolving transient, physiologically or pathologically relevant functional antibody-antigen complexes. Here, we develop a triangular DNA origami framework with site-specifically anchored and spatially organized artificial epitopes to capture transient conformations of immunoglobulin Gs (IgGs) at room temperature. The DNA origami epitopes (DOEs) allows programmed spatial distribution of epitope spikes, which enables direct imaging of functional complexes with atomic force microscopy (AFM). We establish the critical dependence of the IgG avidity on the lateral distance of epitopes within 3–20 nm at the single-molecule level. High-speed AFM imaging of transient conformations further provides structural and dynamic evidence for the IgG avidity from monovalent to bivalent in a single event, which sheds light on various applications including virus neutralization, diagnostic detection and cancer immunotherapy.

Suggested Citation

  • Ping Zhang & Xiaoguo Liu & Pi Liu & Fei Wang & Hirotaka Ariyama & Toshio Ando & Jianping Lin & Lihua Wang & Jun Hu & Bin Li & Chunhai Fan, 2020. "Capturing transient antibody conformations with DNA origami epitopes," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16949-4
    DOI: 10.1038/s41467-020-16949-4
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    Cited by:

    1. Anna Huhn & Daniel Nissley & Daniel B. Wilson & Mikhail A. Kutuzov & Robert Donat & Tiong Kit Tan & Ying Zhang & Michael I. Barton & Chang Liu & Wanwisa Dejnirattisai & Piyada Supasa & Juthathip Mongk, 2025. "The molecular reach of antibodies crucially underpins their viral neutralisation capacity," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    2. Xuanyu Nan & Yujie Li & Rui Zhang & Ruoke Wang & Niannian Lv & Jiayi Li & Yuanfang Chen & Bini Zhou & Yangjunqi Wang & Ziyi Wang & Jiayi Zhu & Jing Chen & Jinqian Li & Wenlong Chen & Qi Zhang & Xuanli, 2024. "Exploring distinct modes of inter-spike cross-linking for enhanced neutralization by SARS-CoV-2 antibodies," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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