Year: 2020
Type: article
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.
Source: Nature Communications
Authors: Ping Zhang, Xiaoguo Liu, Pi Liu, Fei Wang, Hirotaka Ariyama, Toshio Ando, Jianping Lin, Lihua Wang, Jun Hu, Bin Li, Chunhai Fan
Institutions: Chinese Academy of Sciences, Shanghai Institute of Applied Physics, University of Chinese Academy of Sciences, Shanghai Jiao Tong University, Nankai University, Tianjin Institute of Industrial Biotechnology, State Key Laboratory of Medicinal Chemical Biology, Southern Medical University, Kanazawa University, Nano Life Science Institute, Kanazawa University, Shanghai Advanced Research Institute, East China Normal University, Renji Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,380
Funders: Innovative Research Team of High-level Local University in Shanghai, National Natural Science Foundation of China, Ministry of Science and Technology of the People's Republic of China, Shanghai Jiao Tong University, Japan Society for the Promotion of Science, National Key Research and Development Program of China
OpenAlex ID: W3036726016