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Capturing transient antibody conformations with DNA origami epitopes

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 functiona...

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Autores principales: Zhang, Ping, Liu, Xiaoguo, Liu, Pi, Wang, Fei, Ariyama, Hirotaka, Ando, Toshio, Lin, Jianping, Wang, Lihua, Hu, Jun, Li, Bin, Fan, Chunhai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305102/
https://www.ncbi.nlm.nih.gov/pubmed/32561744
http://dx.doi.org/10.1038/s41467-020-16949-4
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author Zhang, Ping
Liu, Xiaoguo
Liu, Pi
Wang, Fei
Ariyama, Hirotaka
Ando, Toshio
Lin, Jianping
Wang, Lihua
Hu, Jun
Li, Bin
Fan, Chunhai
author_facet Zhang, Ping
Liu, Xiaoguo
Liu, Pi
Wang, Fei
Ariyama, Hirotaka
Ando, Toshio
Lin, Jianping
Wang, Lihua
Hu, Jun
Li, Bin
Fan, Chunhai
author_sort Zhang, Ping
collection PubMed
description 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.
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spelling pubmed-73051022020-06-22 Capturing transient antibody conformations with DNA origami epitopes Zhang, Ping Liu, Xiaoguo Liu, Pi Wang, Fei Ariyama, Hirotaka Ando, Toshio Lin, Jianping Wang, Lihua Hu, Jun Li, Bin Fan, Chunhai Nat Commun Article 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. Nature Publishing Group UK 2020-06-19 /pmc/articles/PMC7305102/ /pubmed/32561744 http://dx.doi.org/10.1038/s41467-020-16949-4 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Ping
Liu, Xiaoguo
Liu, Pi
Wang, Fei
Ariyama, Hirotaka
Ando, Toshio
Lin, Jianping
Wang, Lihua
Hu, Jun
Li, Bin
Fan, Chunhai
Capturing transient antibody conformations with DNA origami epitopes
title Capturing transient antibody conformations with DNA origami epitopes
title_full Capturing transient antibody conformations with DNA origami epitopes
title_fullStr Capturing transient antibody conformations with DNA origami epitopes
title_full_unstemmed Capturing transient antibody conformations with DNA origami epitopes
title_short Capturing transient antibody conformations with DNA origami epitopes
title_sort capturing transient antibody conformations with dna origami epitopes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305102/
https://www.ncbi.nlm.nih.gov/pubmed/32561744
http://dx.doi.org/10.1038/s41467-020-16949-4
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