Capturing transient antibody conformations with DNA origami epitopes

Ping Zhang, Xiaoguo Liu, Pi Liu, Fei Wang, Hirotaka Ariyama, Toshio Ando, Jianping Lin, Lihua Wang, Jun Hu (), Bin Li () and Chunhai Fan ()
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Ping Zhang: University of Chinese Academy of Sciences
Xiaoguo Liu: Institute of Translational Medicine
Pi Liu: Nankai University
Fei Wang: Institute of Translational Medicine
Hirotaka Ariyama: Kanazawa University
Toshio Ando: Kanazawa University
Jianping Lin: Nankai University
Lihua Wang: Chinese Academy of Sciences
Jun Hu: University of Chinese Academy of Sciences
Bin Li: University of Chinese Academy of Sciences
Chunhai Fan: Institute of Translational Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-16949-4

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